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The Cardiovascular System:
Anatomy, Physiology, Pathology
T
hough most of the systems that make up the human
body are more or less necessary for normal, healthy
function, if not for survival, the circulatory system is
uniquely essential. Virtually all tissues except epidermis,
cartilage, and dental enamel are richly supplied with blood
vessels that deliver oxygen and nutrients and carry away carbon dioxide and other waste products.
Significant or prolonged interruption of the blood supply
to a tissue, organ, or limb usually results in irreversible damage to at least some cells, and may compromise the entire
structure. If a vital organ such as the heart, brain, or kidney
is involved, death may ensue. Diseases that affect the circulation are thus among the most significant and serious of all,
and their prevention and treatment play a major role in the
modern practice of medicine.
Within recent years, biomedical research has clarified the
intricacies of cardiovascular physiology; gained a fuller understanding of the mechanisms underlying hypertension, atherosclerosis, and congestive heart failure; developed sophisticated
diagnostic methods for these and other conditions; and provided increasingly effective methods of prevention and treatment. A brief review of cardiac anatomy and physiology will
pave the way for a clearer understanding of these issues.
Cardiovascular Anatomy and Physiology
The heart consists of two pumps working synchronously
side by side and sharing an inner wall in common. Although
these two pumps are intimately allied in structure and function, each handles a different component of the total blood
volume, and (except in the presence of structural abnormality)
mixing of the two circulations does not occur.
Each pump consists of two chambers: a relatively thinwalled collecting chamber, or atrium, and the pump proper,
or ventricle. Each contraction of a ventricle propels blood
through a single large vessel, which branches into increasingly
smaller vessels and eventually into vessels of microscopic caliber called capillaries. Each ventricle is equipped with two
valves. One of these prevents backflow of blood into the
atrium when the ventricle contracts, and the other prevents
backflow of expelled blood into the ventricle while it is
relaxed and refilling for the next contraction.
Contraction of a chamber is called systole, and relaxation
is called diastole. Systole occurs when a wave of electrical
activity, beginning at the pacemaker (sinoatrial node) in the
right atrium, spreads over the heart muscle, stimulating first
by John H. Dirckx, M.D.
the atria and then the ventricles to contract. During the fraction of a second that elapses before the next impulse from the
pacemaker, the heart muscle relaxes in diastole and refilling
of the chambers occurs.
Venous blood, low in oxygen and high in carbon dioxide,
is collected by the superior and inferior venae cavae and delivered to the right atrium and hence to the right ventricle. Right
ventricular systole sends this blood through the pulmonary
artery to the lungs, in whose capillaries the blood picks up
fresh oxygen from inspired air and discharges excess carbon
dioxide into air that is about to be expired. During systole the
tricuspid valve prevents blood from leaking back into the right
atrium, and during the succeeding diastole the pulmonic valve
keeps blood from leaking back into the right ventricle.
Oxygenated and purified blood is returned to the heart by the
pulmonary veins, which deliver it to the left atrium.
Passing from the left atrium to the left ventricle, the blood
is now pumped through the aorta into the arteries of the systemic circulation. During left ventricular systole, the mitral
valve prevents blood from being driven back into the left
atrium; during diastole, the aortic valve prevents blood from
leaking back into the ventricle. The arteries branch into
increasingly smaller vessels and eventually break up into capillaries in the tissues, where oxygen is released and carbon
dioxide and other wastes are taken up. The blood then passes
through peripheral veins back to the venae cavae and the circuit is complete.
Hypertension
Hypertension means abnormal elevation of the blood
pressure; specifically, a transitory or persistent elevation of
the pressure of the blood in the arteries of the systemic circulation to a level that can induce cardiovascular damage.
(Pulmonary hypertension, affecting the pulmonary arteries,
which carry blood to the lungs from the right ventricle, is a
separate disorder usually related to disease of the lungs, pulmonary vasculature, or mitral valve.)
Hypertension is a major cause of cardiovascular disease
and premature death in Western (industrialized) societies. The
annual toll of deaths due directly to hypertension in the United
States is about 35,000, and it is recognized as a contributing
factor in another 180,000 deaths. Persons with hypertension
have a 3-fold increase in the risk of heart attack and a 7- to
10-fold increase in the risk of stroke. One fourth of the population of the U.S. (and one half of persons over age 60) have
John H. Dirckx, M.D., The Cardiovascular System: Anatomy, Physiology, Pathology
The SUM Program Cardiology Transcription Unit, 2nd ed. ©2011, Health Professions Institute, www.hpisum.com
The annual toll of deaths due directly
to hypertension in the United States is
about 35,000, and it is recognized as a
contributing factor in another 180,000
deaths.
significant elevation of blood pressure, but only about one
third of persons so affected are aware of the condition and are
receiving treatment. The prevalence of hypertension and the
risk of complications are considerably higher in African
Americans.
Hypertension is defined arbitrarily as systolic blood pressure above 140 mmHg or diastolic blood pressure above 90
mmHg. The systolic pressure is the highest pressure reached
by the blood in the large arteries with each beat of the heart,
while the diastolic pressure is the lowest level to which the
pressure drops between beats of the heart. The aorta and its
branches and sub-branches—the named arteries of the body—
are not rigid pipes, but are normally highly elastic structures.
This helps to keep the blood flowing at a smoother rate instead
of allowing it to be propelled through the arteries in a series
of jerks. To put it another way, the elasticity of the arteries
minimizes the difference (called the pulse pressure) between
systolic and diastolic pressures.
As each contraction of the left ventricle propels blood into
the arterial system, the vessels expand to accommodate the
sudden increased load of blood. (This rhythmic bulging
accounts for the “pulse,” synchronous with the heartbeat, that
can be felt in peripheral arteries.) Then, during diastole, as
the left ventricle relaxes and refills, the stretched arterial walls
rebound, keeping the blood moving forward through the circulation until the next systole occurs. In this way the aorta and
larger arteries act as a sort of auxiliary heart, briefly storing
some of the kinetic energy of each ventricular contraction and
then releasing it while the ventricle is filling in preparation for
its next contraction.
The pressure of the blood depends on an interplay of
many factors, but two of these are of primary importance: the
rate and force of ventricular contractions and the resistance of
the arteries against which the heart has to work in order to
maintain adequate flow in tissue capillaries. Arterial resistance
depends on the net cross-sectional area of the large and
medium-sized arteries, and this net area varies with the tone
or state of contraction of the muscular layers of these arteries.
The maintenance of normal blood pressure depends on a
complex interaction, not yet fully understood, of neural and
hormonal control mechanisms. Hypertension results when
these control mechanisms become dysregulated in any of various ways.
The adrenergic system is concerned with maintaining normal blood flow to vital structures from minute to minute by
meeting acute, short-term needs. Challenges as variable as
standing up from a recumbent or sitting position, dehydration
due to vomiting and diarrhea, and severe hemorrhage can all
pose acute threats to the adequacy of blood flow to the brain
and heart. When blood pressure sensors (baroreceptors) in
large arteries detect a drop in pressure, sympathetic nerve
fibers to the heart automatically increase the rate and force of
cardiac contractions.
Meanwhile, sympathomimetic hormones (epinephrine,
norepinephrine, dopamine, serotonin) are released from the
suprarenal glands and other glandlike structures to boost and
regulate blood flow, not only by stimulating the heart but also
by acting on the muscular layers of arteries, dilating those that
supply vital organs while constricting or shutting down those
to less critical areas such as the skin and the digestive system.
A neoplasm that produces serotonin (carcinoid tumor) or epinephrine-like substances (pheochromocytoma) can cause intermittent or sustained elevation of blood pressure, but these are
relatively rare causes of hypertension.
The renin-angiotensin-aldosterone system provides
longer-term regulation of blood pressure by offsetting less
acute variations in blood flow to vital tissues. The action of
this system involves a complex interaction of hormones and
enzymes produced at widely differing sites. Angiotensinogen,
a globulin formed in the liver, is normally present in blood
and tissues but performs no physiologic function. That is, it is
a precursor substance that must be chemically converted
before it becomes active.
The first step of this conversion takes place under the
influence of renin, an enzyme produced in the kidney. The
release of renin can be triggered in various ways: by a drop
in systemic blood pressure, as detected by baroreceptors; by
a decline in the amount of urine being processed by the renal
tubules (an indirect indication of diminished renal blood flow);
or even by a change in the sodium chloride concentration of
renal tubular fluid. Under the action of renin, angiotensinogen
is converted to angiotensin I.
This substance, too, is just an intermediary metabolite.
Only when angiotensin I is converted to angiotensin II does
the system begin to have an impact on blood pressure and
electrolyte balance. This conversion is triggered by angiotensin-converting enzyme (ACE), a glycoprotein produced in
various tissues, principally the lung. Angiotensin II is a powerful and wide-ranging agent, which raises systemic blood
pressure by acting directly on the peripheral circulation as a
vasoconstrictor, and which also stimulates the cortices of the
suprarenal glands to secrete aldosterone, a hormone that promotes retention of sodium. Angiotension II has other functions, such as promotion of cell proliferation and migration,
that do not concern us here.
Early in the twentieth century it was discovered that
obstruction of a renal artery by disease (or ligation of a renal
artery in an experimental animal) can induce hypertension.
We now know that this abnormal elevation of blood pressure
results from an overproduction of renin by the diseased kidney, which responds to local ischemia in the same way that it
would respond to a sustained reduction in systemic blood pressure. An occasional case of hypertension is found to be due
to a lesion in a renal artery. That is the reason why physicians
listen with a stethoscope over the flanks for a bruit that might
John H. Dirckx, M.D., The Cardiovascular System: Anatomy, Physiology, Pathology
The SUM Program Cardiology Transcription Unit, 2nd ed. ©2011, Health Professions Institute, www.hpisum.com
indicate stenosis (narrowing) of a renal artery, particularly
when assessing a patient with hypertension.
When chronic elevation of blood pressure is traced to
renal ischemia or a hormone-producing tumor, the condition
may be reversible by surgery. But such cases of secondary
hypertension make up fewer than 10% of the total; the rest
are termed essential hypertension. Essential hypertension is
currently believed to result from a complex derangement,
genetically induced, in the renin-angiotensin-aldosterone system. Persons with essential hypertension have elevated peripheral vascular resistance and they retain excessive sodium.
Moreover, drugs that reduce peripheral resistance and
enhance the renal excretion of sodium are useful in correcting
essential hypertension. Drugs that block the action of
angiotensin-converting enzyme (ACE inhibitors) or of
angiotensin II (angiotensin II receptor inhibitors) work even
better.
It has been recognized for about one hundred years that
uncontrolled chronic hypertension is associated with disease of
both the heart and the arteries of the systemic circulation.
Sustained elevation of systolic pressure overworks the heart
and can lead to ventricular dilatation (stretching of the ventricular wall due to chronic overfilling), hypertrophy (compensatory overgrowth of ventricular muscle), or cardiac
failure (discussed below).
In addition, chronic hypertension leads to loss of tone and
elasticity in arteries, and can aggravate arterial changes due to
aging or atherosclerosis (also discussed below). Among the
arteries that may be so affected are those of the retina. This
is significant partly because uncontrolled hypertension can
lead to visual impairment. But of broader importance is the
fact that the retinal vessels can easily be examined with an
ophthalmoscope, unless the patient has severe cataracts.
Examination of the ocular fundi or “eye grounds” is part
of the routine physical examination of an adult, and can yield
important information about general vascular health as well as
the presence and severity of hypertension. The four KeithWagener-Barker stages of hypertensive retinopathy are:
Grade 1—Focal or diffuse narrowing of arteriolar caliber
due to spasm.
Grade 2—Arteriolar diameter less than 50% of that of
corresponding venules; “silver wire,” “copper wire,” or
“pipestem” appearance of arterioles, indicating structural
changes in vessel walls.
Grade 3—In addition to the above changes, retinal hemorrhages or exudates. (As used in this context, exudate is
something of a misnomer. A retinal exudate is a whitish spot
of variable size, shape, and composition—usually a deposit of
lipid material at a site of old hemorrhage or infarction.)
Grade 4—In addition to the above, papilledema (swelling
of the optic nerve head).
While the effects of hypertension on retinal vessels provide valuable diagnostic information, the impact of the disease
on arteries supplying vital structures is of far greater importance. The adverse effects of chronic hypertension on the cardiovascular system are complex and cumulative. For example,
Hypertension is defined arbitrarily as
systolic blood pressure above 140 mmHg or
diastolic blood pressure above 90 mmHg.
damage to renal vasculature caused by hypertension can augment the overproduction of renin, leading to more severe
hypertension and accelerated progression of disease.
Known risk factors for essential hypertension include a
family history of hypertension, African American ethnicity,
age over 60, the postmenopausal state, overweight, a sedentary lifestyle, excessive intake of dietary sodium, excessive
use of alcohol, and chronic emotional stress. It is currently
recognized that, for many persons with essential hypertension,
blood pressure elevation is just one feature of a complex disorder called the metabolic syndrome (discussed below). This
syndrome, induced by an interplay of genetic and environmental factors, includes obesity, abnormal glucose and lipid
metabolism, insulin resistance, diminished arterial compliance, accelerated atherogenesis, and renal disease.
Although extremely high diastolic pressure can sometimes be associated with headache, dizziness, or even seizures
and coma, uncomplicated hypertension seldom causes any
symptoms at all. For that reason, the diagnosis is usually
made incidentally, during screening of seemingly healthy persons or those who are being examined or treated for some
other condition.
Statistics show that the early detection and aggressive
treatment of hypertension can reduce morbidity and mortality
associated with this condition. For example, control of hypertension reduces the risk of stroke by 30-50%. Modern standards of medical practice require vigorous efforts to identify
hypertension, particularly in persons at high risk, and early
and aggressive treatment of the condition when it is found.
Current treatment protocols favor a stepped approach: first
lifestyle changes (weight loss if appropriate, regular aerobic
exercise, restriction of sodium and alcohol intake, and reduction of emotional stress when possible), then drugs gradually
increasing in potency (and price tag and potential side effects).
Drugs used to treat hypertension include diuretics that
promote renal excretion of sodium; beta-adrenergic and calcium channel blockers, which blunt the effects of sympathetic
nerve stimuli and of circulating adrenergic agents on heart
action and vascular tone; angiotensin-converting enzyme
(ACE) inhibitors and angiotensin II receptor antagonists;
alpha-1 adrenergic antagonists; centrally acting alpha-agonists; and others.
Atherosclerosis
As early as the nineteenth century, pathologists recognized
that the arteries of older persons often lose their elasticity and
become narrowed in caliber. They also observed that these
degenerative changes, which they termed arteriosclerosis (literally ‘hardening of the arteries’), are often associated with
ischemia of the tissues supplied, and are thus the underlying
John H. Dirckx, M.D., The Cardiovascular System: Anatomy, Physiology, Pathology
The SUM Program Cardiology Transcription Unit, 2nd ed. ©2011, Health Professions Institute, www.hpisum.com
mechanism of many serious health problems, including
myocardial ischemia (causing angina, cardiac failure, and
myocardial infarction), cerebrovascular disease (causing
stroke and dementia), and peripheral vascular disease (causing
intermittent claudication and gangrene of extremities).
During the twentieth century, advances in microscopy
and biochemistry led to the discovery that most cases of arteriosclerosis are due to deposits of lipid material (cholesterol)
in the walls of the arteries affected. This commonest type of
arteriosclerosis was termed atherosclerosis (from a Greek
word meaning ‘gruel’, referring to the gritty, pasty consistency of the lipid deposits).
Atherosclerosis (Figure 1) is characterized by the occurrence of irregularly distributed lipid deposits (atheromata or
atheromas; singular, atheroma) in the innermost layer (tunica
intima) of large and medium-sized arteries. With the passage
of time these lesions become fibrous, like scar tissue, and may
even calcify; hence the progressive loss of elasticity. Atheromatous deposits tend to grow slowly and intermittently, but in
time they can cause significant reduction in the caliber of
affected arteries, with impairment of blood flow and clinical
consequences that depend on the tissues supplied.
Early theories of the causation of atherosclerosis viewed
it as a degenerative process and traced it to an elevation of circulating cholesterol, which was assumed to result from excessive dietary intake of cholesterol. We now realize that
inflammation plays a more important role than degeneration
Figure 1
Atherosclerosis
Source: National Heart Lung and Blood Institute, National Institutes of Health. Accessed from Wikipedia Commons.
in the atherosclerotic process, and that elevation of the cholesterol level usually results from an inborn metabolic flaw
rather than from consumption of too much cholesterol in the
diet.
Cholesterol is a complex lipid (fatty) molecule that serves
as a building block for many important substances, including
the steroid hormones (cortisol and the sex hormones), bile
salts, and certain constituents of cell membranes. Some cholesterol is found in every cell in the body. But even though it
is an essential component of all tissues, it is not considered a
nutrient, because it is continually being synthesized from simpler substances by the liver and other tissues.
Cholesterol is found in virtually all foods from animal
sources—meats, poultry, fish, eggs, milk, and dairy products.
It is especially abundant in fatty meats, whole milk, and egg
yolk. Although a high intake of cholesterol-containing foods
can raise the serum cholesterol to unhealthful levels, dietary
cholesterol is probably not of major importance for most persons in the genesis of atherosclerosis. Moreover, dietary
restrictions are only slightly helpful in reducing an abnormally
high cholesterol level. Of far greater importance in the development of hypercholesterolemia and its treatment is the role
of inherited imbalances in the proportion of low- and highdensity lipoproteins.
As noted above, current theories regard atherosclerosis
chiefly as an inflammatory rather than a degenerative process.
Atheromata are more likely to develop at areas of turbulent
flow within an artery, such as at a bifurcation. The earliest
stage in the process that can be recognized on histopathologic
study is the appearance, in the lining (tunica intima) of an
artery, of so-called foam cells. These are macrophages (tissue
cells that phagocytize dead cells and other debris) that look
foamy because they are stuffed with cholesterol.
The presence of this material in a place where it doesn’t
belong elicits local inflammation, mediated by various tissue
factors, including interleukins, cell adhesion molecules, and
platelet factors. Circulating monocytes and lymphocytes stick
to and penetrate the lining of the artery at the site of the cholesterol deposit. Smooth muscle cells in the underlying muscular coat (tunica media) of the artery proliferate to form a
plaque, which continues to enlarge as more cholesterol is
deposited. Fibrosis, a scar-like formation of connective tissue
fibers within the plaque, eventually occurs, and as a final
stage the plaque may calcify.
The expansion of an atheromatous plaque leads to stenosis (reduction in caliber) of the artery, which can culminate in
occlusion (complete obstruction to blood flow), with ischemia
(impairment of blood supply) or infarction (irreversible damage) of tissues supplied by it. Besides blocking blood flow, a
plaque can break down and ulcerate, releasing fragments
(emboli) into the circulation, which can cause obstruction of
a smaller arterial branch distally.
An atheromatous plaque can also become the site of
thrombosis (local formation of a blood clot), and besides further reducing vascular caliber this too can result in embolization of distal vessels. In addition, inflammatory and
degenerative changes in and around the plaque can lead to local
John H. Dirckx, M.D., The Cardiovascular System: Anatomy, Physiology, Pathology
The SUM Program Cardiology Transcription Unit, 2nd ed. ©2011, Health Professions Institute, www.hpisum.com
hemorrhage or dissection (separation or splitting of layers of
the arterial wall as blood, under normal or elevated pressure,
forces it way through damaged tissue).
The diagnosis of atherosclerosis is based on history and
physical examination, augmented by angiography, Doppler
ultrasonography, and other imaging studies. Treatment is
largely mechanical: balloon stretching, laser ablation, or surgical removal of plaques, and various bypass and grafting procedures. More specific information on the diagnosis and
treatment of coronary atherosclerosis will be presented later.
Well-established risk factors for atherosclerosis are male
sex, advancing age, the postmenopausal state, a family history
of atherosclerosis, cigarette smoking, elevation of plasma total
cholesterol and low-density lipoprotein (LDL) cholesterol,
hypertension, diabetes mellitus, overweight, and a sedentary
lifestyle. Other risk factors detectable by biochemical testing
include elevation of plasma triglycerides, fasting insulin, fibrinogen, C-reactive protein, amyloid A, interleukin-6,
apolipoproteins A and B, lipoprotein (a), and homocysteine.
The prevention of atherosclerosis is a high-priority objective for modern medicine. Measures of proven value include
regular vigorous (anerobic) exercise, a diet low in fat and cholesterol, maintenance of a healthful weight, and avoidance of
tobacco. Drug therapy is indicated for diabetes mellitus and
hypercholesterolemia.
Myocardial Infarction
Myocardial infarction (MI), also known as coronary
thrombosis and heart attack, is defined as death (irreversible
damage) of a segment of heart muscle (myocardium) caused
by obstruction to blood flow in one or more branches of the
coronary system. Myocardial infarction is currently recognized as the most common cause of death in this country.
About 800,000 persons annually sustain first heart attacks,
with a mortality rate of 30%, and 450,000 persons sustain
recurrent heart attacks, with a mortality rate of 50%.
The usual cause of MI is formation of a thrombus in a
coronary artery (Figure 2) at the site of an atherosclerotic
plaque. Less frequent causes are anatomic anomalies or
inflammatory disease (vasculitis) involving the coronary arteries and arterial spasm induced by drugs, particularly cocaine.
At least 80% of persons sustaining myocardial infarction
have no prior history of angina pectoris, and in 20% the diagnosis is missed because symptoms are either absent (“silent
infarction”) or are blamed on something else. Some 20% of
persons sustaining MI die before reaching a hospital.
Nowadays everyone who has completed training in adult
CPR knows the symptoms and signs of a heart attack. It may
therefore seem surprising that the very first patient in whom
myocardial infarction was diagnosed before death was
reported as recently as 1912 by the American physician James
B. Herrick. The classical symptoms of myocardial infarction
are crushing anterior chest pain radiating into the neck, shoulder, or arm, lasting more than 30 minutes, and not relieved
by nitroglycerin.
The classical symptoms of myocardial
infarction are crushing anterior chest pain
radiating into the neck, shoulder, or arm,
lasting more than 30 minutes, and not
relieved by nitroglycerin.
Recent studies have identified important gender differences in the collateral symptoms of MI. Although chest pain
is the most common symptom reported by both men and
women, diaphoresis is more likely to occur in men, while
women are more likely to complain of neck, jaw, or back
pain, nausea, vomiting, and dyspnea.
Clear-cut evidence of acute infarction may not be obtainable during the first 6 hours in as many as one half of patients;
hence the need for close observation even in cases where the
diagnosis seems doubtful. Physical examination is often unremarkable but may detect soft heart sounds, an atrial gallop
rhythm (4th heart sound), or a pericardial friction rub.
Classical electrocardiographic signs are ST segment elevation
(later changing to depression) and T wave inversion in leads
recording electrical activity in the infarcted segment of
myocardium. Deep Q waves indicate transmural (“all the way
through the muscular wall”) damage and a graver prognosis.
Diagnosis may be confirmed by elevation in serum levels of
myoglobin, lactic dehydrogenase, the MB isoenzyme of creatine kinase, and troponins.
Figure 2
Coronary Artery
Source: National Heart Lung and Blood Institute, National Insti tutes of Health. Accessed from Wikipedia Commons.
John H. Dirckx, M.D., The Cardiovascular System: Anatomy, Physiology, Pathology
The SUM Program Cardiology Transcription Unit, 2nd ed. ©2011, Health Professions Institute, www.hpisum.com
The full expression congestive heart
failure refers to the elevation of central
venous pressure that typically accompanies
. . . reduction in pumping efficiency.
Acute myocardial infarction can cause death by a variety
of mechanisms: cardiac arrest, ventricular fibrillation (ineffectual twitching of damaged heart muscle instead of normal
contractions), cardiogenic shock (inability of the heart to
maintain adequate blood flow for vital functions), congestive
heart failure (discussed below), rupture of a papillary muscle
with resulting malfunction of the aortic or pulmonic valve, or
even rupture of a ventricle (cardiorrhexis).
The standard treatment of myocardial infarction includes
admission to a coronary care unit with continuous cardiac
monitoring and the administration of a narcotic analgesic for
pain, oxygen by inhalation to boost myocardial oxygenation,
a beta-blocker, an ACE inhibitor, an anticoagulant (aspirin
orally and heparin by injection), and a thrombolytic agent.
During the past decade, thrombolytic therapy (the intravenous administration of an agent intended to restore circulation by dissolving a thrombus in an artery) has reduced the
mortality of acute myocardial infarction by 20-40%. Under
favorable circumstances, about 50% of patients with acute MI
will have patent coronary arteries 90 minutes after treatment.
Best results are achieved when the agent is given within 100
minutes after the onset of symptoms.
Thrombolytic agents break down the fibrin in a clot by
activating plasminogen, a naturally occurring substance
involved in clotting mechanisms. Agents most often used to
treat MI are tissue plasminogen activator (TPA), which is synthesized by recombinant DNA, and streptokinase, an enzyme
produced by streptococci. Although streptokinase is sometimes chosen instead of TPA because it is less expensive, TPA
is more effective.
Hemorrhage is a major risk with thrombolytic therapy.
Contraindications include active or recent bleeding of any
cause, recent surgery, prolonged or traumatic cardiopulmonary resuscitation, and pregnancy.
When evidence of acute myocardial ischemia persists
despite medical therapy, angiography may be done to confirm
and localize coronary occlusion. Emergency PTCA performed
within two hours after the onset of pain in acute myocardial
infarction yields a lower mortality rate than thrombolytic therapy and lower rates of nonfatal reinfarction and hemorrhagic
stroke.
Congestive Heart Failure
Congestive heart failure is an extremely common complication of a broad range of disorders, not all of them primarily affecting the heart. In this country alone, congestive heart
failure is the reason for about one million hospital admissions
annually, and ranks number one among discharge diagnoses
for hospitalized patients over 65. In persons over 80, the
prevalence of chronic heart failure is about 10%.
The term heart failure (Figure 3) has a more restricted
meaning than lay persons sometimes suppose; it certainly is
not synonymous with cardiac arrest. But although physicians
define heart failure as “an acute or chronic impairment of the
ability of the heart to function efficiently as a pump,” it is
becoming increasingly evident that this disorder is far more
complex than if the failing heart were simply a piece of wornout machinery.
Cardiologists now recognize that heart failure is a spectrum of clinical states having in common a reduction in the
pumping efficiency of the heart but varying widely in symptoms, signs, and impact on normal function. The full expression congestive heart failure refers to the elevation of central
venous pressure that typically accompanies this reduction in
pumping efficiency.
The many conditions that can culminate in congestive
heart failure can be divided into two large classes: those that
directly impair the contractile force of the heart, and those that
Figure 3
Heart Failure
Source: Wikipedia Commons.
John H. Dirckx, M.D., The Cardiovascular System: Anatomy, Physiology, Pathology
The SUM Program Cardiology Transcription Unit, 2nd ed. ©2011, Health Professions Institute, www.hpisum.com
place an excessive burden on the heart. Both types can occur
together in the same person. Among disorders that curtail the
pumping power of heart muscle, coronary artery disease is by
far the most common, but intrinsic disease of the myocardium
due to infection, autoimmune disease, or deficiency states can
also result in primary pump failure.
Disorders that can induce failure by overworking a normal heart include hypertension, congenital or acquired disease
of a heart valve, arteriovenous fistula (an abnormal communication somewhere in the circulation through which arterial
blood is shunted directly into the venous circulation), severe
anemia, and hyperthyroidism.
In cardiac failure resulting from coronary artery disease
and hypertension, cardiac output (that is, the amount of blood
pumped into the aorta with each contraction of the left ventricle) is reduced; hence the resulting disturbance in cardiovascular dynamics is referred to as low-output failure. In
contrast, cardiac output may be normal or increased in failure
due to anemia, arteriovenous fistula, or thyrotoxicosis, hence
the term high-output failure.
Cardiac output can be assessed or measured in various
ways. The stroke volume is the volume of blood expelled from
the ventricle during systole; the ejection fraction (expressed as
a percent) is that proportion of the blood in the ventricle at the
end of diastole that is actually expelled during systole. The
pulse pressure (which, as mentioned earlier, is the difference
between systolic and diastolic blood pressures) is typically
reduced in low-output failure and increased in high-output
failure.
Certain conditions (pulmonary hypertension, mitral stenosis, tricuspid regurgitation) are associated with primarily right
ventricular failure. But most discussions of cardiac failure,
including this one, emphasize the left ventricle, because
impairment of pumping efficiency in the left side of the heart
has more profound and serious effects on cardiovascular
dynamics. It is nonetheless true that coronary artery disease,
the commonest cause of congestive failure, can affect either
ventricle separately, or both of them in varying degrees.
Moreover, because the right and left ventricles operate in tandem and form parts of a single circuit, severe failure of one
will eventually diminish the efficiency of the other.
Fifty years ago, theories of the pathophysiology of heart
failure made a sharp distinction between “forward” and
“backward” failure. Forward failure denotes the inability of
the left ventricle to pump enough blood to meet the needs of
tissues; backward failure refers to the buildup of pressure in
the ventricle that results from its inability to distend adequately during diastolic filling. This rise of pressure in the left
ventricle, extending “backward” to raise the pressure within
the pulmonary venous circulation, is responsible for the dyspnea and reduction in exercise tolerance that are among the
most conspicuous features of heart failure. Similarly, backward failure of the right ventricle raises the pressure in the
peripheral venous system, causing venous distention and
edema of the viscera and extremities. Hence it is this backward component of the process that results in the congestive
aspect of heart failure.
Even with aggressive treatment, the fiveyear survival rate for persons with congestive heart failure is only 50%. Death most
commonly results from progressive ventricular dysfunction, arrhythmia, or thromboembolism.
In modern cardiology, the distinction between forward
and backward failure is viewed as a purely conceptual one.
The fully developed syndrome of heart failure includes both
of these elements as coordinate and interactive aspects of the
same basic phenomenon. Similarly, the validity of older distinctions between right and left heart failure and between systolic and diastolic heart failure have been called into question.
A syndrome of isolated or predominantly diastolic failure
does, however, occur in some persons. In this disorder,
affecting particularly elderly patients with hypertension and
atherosclerosis, the ejection fraction may be normal, but left
atrial and pulmonary venous pressures are elevated because
diastolic filling of the left ventricle is impaired.
Whereas older concepts of congestive heart failure tended
to view the failing heart as a faltering or deteriorating mechanism in isolation from other bodily systems, we now know
that neural and hormonal factors play a crucial role in the
development of the syndrome. The drop in systemic blood
flow that occurs with low-output failure triggers sympathetic
responses (increase in heart rate and myocardial contractility,
peripheral vasoconstriction) that only add to the burden of the
failing heart. The renin-angiotensin-aldosterone system, discussed earlier in connection with hypertension, also plays an
important role in the pathophysiology of congestive heart failure. Reduction in renal blood flow leads to activation of this
system, with resultant further peripheral vasoconstriction and
retention of sodium and water.
Symptoms typical of left ventricular failure are dyspnea,
cough, and reduced exercise tolerance. Shortness of breath
may occur at rest or only with exertion. Two types of dyspnea are especially characteristic of left heart failure, though
they can also occur in other conditions. Orthopnea is shortness of breath in the recumbent position, relieved by sitting
up; paroxysmal nocturnal dyspnea (PND) is an attack of
shortness of breath that awakens the patient from sleep during
the night.
These symptoms result from the rise of back-pressure in
the pulmonary venous system, which causes pulmonary congestion (vascular engorgement) and interstitial edema (excess
fluid in lung tissues). Severe left ventricular failure can cause
acute pulmonary edema, with transudation of watery fluid into
pulmonary air sacs. This condition, manifested by severe
dyspnea and production of copious frothy sputum, is a medical emergency.
John H. Dirckx, M.D., The Cardiovascular System: Anatomy, Physiology, Pathology
The SUM Program Cardiology Transcription Unit, 2nd ed. ©2011, Health Professions Institute, www.hpisum.com
Limitation of dietary sodium to 2-3
g/day and administration of diuretics, ACE
inhibitors, and beta-blocking agents are
useful in correcting sodium retention and
circulatory overload.
The symptoms of right ventricular failure result from elevation of pressure in systemic veins: swelling of the lower
limbs (dependent edema) and effusion of fluid into the peritoneal cavity (ascites). Squeezing a severely swollen limb with
the fingers may leave impressions that only slowly refill; this
is called pitting edema. When peripheral edema involves the
trunk and upper limbs as well as the lower limbs, the term
anasarca is used. Brawny (“tough”) edema is chronic swelling in which deposition of connective tissue fibers in edema
fluid has caused induration.
Physical findings in the patient with congestive heart failure depend on the severity and duration of failure as well as
its underlying cause and the presence of concomitant disorders. Examination of the heart generally reveals tachycardia,
cardiac dilatation, a weak first heart sound, and a prominent
fourth heart sound (protodiastolic gallop). The latter two findings reflect a faltering in the contractile force and pumping
efficiency of the ventricles.
On auscultation of breath sounds, the examiner hears
crepitant rales (crackling sounds like those made by crumpling
a piece of cellophane) caused by bubbling of air through free
edema fluid in small air passages. Systemic venous engorgement may be manifested by distention of the jugular veins,
enlargement of the liver (hepatomegaly), and a fluid wave on
palpation of the abdomen due to ascites. Hepatojugular reflux
is a visible wave of increased engorgement in the jugular veins
after manual compression of the swollen liver.
The chest x-ray of a patient with congestive heart failure shows cardiac dilatation and often Kerley B lines (short
radiopaque streaks indicating edema in interalveolar septa).
Pleural effusion (free edema fluid in the pleural space) may
cause blunting of the costophrenic sulci (the sharp angles
formed by the chest wall and the peripheral rim of the
diaphragm). In the presence of significant systolic dysfunction, an echocardiogram shows an ejection fraction of 40%
or less.
A system endorsed by the American College of Cardiology and the American Heart Association divides the evolution of heart failure into four stages designated with Roman
letters:
A The subject is at high risk of heart failure because of
an underlying condition such as hypertension or
coronary atherosclerosis, but has no symptoms or
signs of structural heart disease.
B Structural heart disease is present, but without symptoms of heart failure.
C Structural heart disease is present, along with past or
present symptoms of heart failure.
D Refractory heart failure requiring special interventions.
The better-known New York Heart Association Classification distinguishes four levels of functional impairment in
heart failure, designated with Roman numerals:
I
II
III
IV
Asymptomatic.
Symptomatic with moderate exertion.
Symptomatic with minimal exertion.
Symptomatic at rest.
The treatment of chronic congestive heart failure begins
with whatever measures are available to control underlying
factors such as hypertension and coronary artery disease.
Limitation of dietary sodium to 2-3 g/day and administration
of diuretics, ACE inhibitors, and beta-blocking agents are useful in correcting sodium retention and circulatory overload.
Digoxin is a derivative of digitalis (foxglove), an herbal remedy which for many decades was the mainstay of treatment in
congestive failure. Digoxin exerts an inotropic effect (that is,
it directly enhances the contractility of heart muscle) and also
stimulates the vagus nerves, thus slowing the pulse and counteracting inappropriate sympathetic stimulation.
Acute pulmonary edema is treated with morphine, an
intravenous diuretic, sublingual and intravenous nitroglycerin,
and nitroprusside. Acute cardiac failure that is refractory to
these agents sometimes responds to inotropic drugs such as
dobutamine and dopamine.
Even with aggressive treatment, the five-year survival
rate for persons with congestive heart failure is only 50%.
Death most commonly results from progressive ventricular
dysfunction, arrhythmia, or thromboembolism.
John H. Dirckx, M.D., The Cardiovascular System: Anatomy, Physiology, Pathology
The SUM Program Cardiology Transcription Unit, 2nd ed. ©2011, Health Professions Institute, www.hpisum.com