Normal Cardiac Structure
and Function
Ch a p t e r O u t l i n e
Cardiac Anatomy and Histology
Pericardium
Sur ace Anatomy o the Heart
Internal Structure o the Heart
Impulse-Conducting System
Cardiac Innervation
Cardiac Vessels
Histology o Ventricular
Myocardial Cells
Basic Electrophysiology
Ion Movement and Channels
Resting Potential
Action Potential
Re ractory Periods
Impulse Conduction
Normal Sequence o Cardiac
Depolarization
Excitation–Contraction Coupling
Contractile Proteins in the
Myocyte
Calcium-Induced Calcium
Release and the Contractile
Cycle
Introduction to Cardiac Signaling
Systems
β-Adrenergic and Cholinergic
Signaling
Ja cob E. Lemieux
Ela zer R. Edelma n
1
Ga ry R. Stricha rtz
Leona rd S. Lilly
K nowledge o normal structure and unction o the heart is
crucial to understanding diseases that a f ict the cardiovas-
cular system. The purpose o this chapter is to describe the heart’s
basic anatomy, its electrical system, and the cellular and molecular
mechanisms o contraction that allow the heart to serve its critical
unctions.
CARDIAC ANATOMY AND HISTOLOGY
Although the study o cardiac anatomy dates back to ancient
times, interest in this eld has recently gained momentum.
The application o sophisticated cardiac imaging tech-
niques such as coronary angiography, echocardiography,
computed tomography, and magnetic resonance imaging
requires an intimate knowledge o the spatial relationships
o cardiac structures. Such in ormation also proves help-
ul in understanding the pathophysiology o heart disease.
This section emphasizes the aspects o cardiac anatomy
that are important to the clinician—that is, the “ unctional”
anatomy.
Pericardium
The heart and roots o the great vessels are enclosed by a
broserous sac called the pericardium (Fig. 1-1). This struc-
ture consists o two layers: a strong outer brous layer and
an inner serosal layer. The inner serosal layer adheres to the
external wall o the heart and is called the visceral pericar-
dium. The visceral pericardium ref ects back on itsel and
lines the outer brous layer, orming the parietal pericar-
dium. The space between the visceral and parietal layers
contains a thin lm o pericardial f uid that allows the heart
to beat in a minimal- riction environment.
1
2 Chapter 1

The pericardium is attached to the ster- S upe rior Aorta

ve na cava
num and the mediastinal portions o the
right and le t pleurae. Its many connections Pulmona ry
to the surrounding structures keep the peri- a rte ry
cardial sac rmly anchored within the tho-
rax and thereby help to maintain the heart in
He a rt within
its normal position. pe rica rdium
Emanating rom the pericardium in a
superior direction are the aorta, the pulmo- Infe rior
ve na cava Dia phra gm
nary artery, and the superior vena cava (see
Fig. 1-1). The in erior vena cava projects
through the pericardium in eriorly.
FIGURE 1-1. The position of the heart in the chest.
The superior vena cava, aorta, and pulmonary artery
Surface Anatomy of the Heart exit superiorly, whereas the inferior vena cava projects
The heart is shaped roughly like a cone and inferiorly.
consists o our muscular chambers. The
right and le t ventricles are the main pumping chambers. The less muscular right and le t
atria deliver blood to their respective ventricles.
Several terms are used to describe the heart’s sur aces and borders (Fig. 1-2). The apex is
ormed by the tip o the le t ventricle, which points in eriorly, anteriorly, and to the le t. The
base or posterior sur ace o the heart is ormed by the atria, mainly the le t, and lies between
the lung hila. The anterior sur ace o the heart is shaped by the right atrium and ventricle.
Because the le t atrium and ventricle lie more posteriorly, they orm only a small strip o this
anterior sur ace. The inferior sur ace o the heart is ormed by both ventricles, primarily the
le t. This sur ace o the heart lies along the diaphragm; hence, it is also re erred to as the
diaphragmatic sur ace.
Observing the chest rom an anteroposterior view (as on a chest radiograph; see
Chapter 3), our recognized borders o the heart are apparent. The right border is estab-
lished by the right atrium and is almost in line with the superior and in erior venae cavae.
The in erior border is nearly horizontal and is ormed mainly by the right ventricle, with
a slight contribution rom the le t ventricle near the apex. The le t ventricle and a portion
o the le t atrium make up the le t border o the heart, whereas the superior border is
shaped by both atria. From this description o the sur ace o the heart emerges two basic
“rules” o normal cardiac anatomy: (1) right-sided structures lie mostly anterior to their
le t-sided counterparts and (2) atrial chambers are located mostly to the right o their cor-
responding ventricles.

Internal Structure of the Heart

Four major valves in the normal heart direct blood f ow in a orward direction and prevent
backward leakage. The atrioventricular (AV) valves (tricuspid and mitral) separate the atria
and ventricles, whereas the semilunar valves (pulmonic and aortic) separate the ventricles
rom the great arteries (Fig. 1-3). All our heart valves are attached to the brous cardiac
skeleton, which is composed o dense connective tissue. The cardiac skeleton also serves as
a site o attachment or the ventricular and atrial muscles.
The sur ace o the heart valves and the interior sur ace o the chambers are lined by
a single layer o endothelial cells, termed the endocardium. The subendocardial tissue
contains broblasts, elastic and collagenous bers, veins, nerves, and branches o the con-
ducting system and is continuous with the connective tissue o the heart muscle layer, the
myocardium. The myocardium is the thickest layer o the heart and consists o bundles o
 Normal Cardiac Structure and Function 3

Le ft common
Bra chioce pha lic a rte ry ca rotid a rte ry

Le ft s ubclavia n
S upe rior ve na cava a rte ry

As ce nding a orta
Le ft pulmona ry
Right s upe rior a rte ry
pulmona ry a rte ry
Right infe rior Le ft pulmona ry
pulmona ry a rte ry ve ins

Right Pulmona ry trunk

pulmona ry ve ins

Le ft a tria l a ppe nda ge

Right a tria l
a ppe nda ge Le ft ve ntricle
Right a trium

Infe rior ve na cava

Right ve ntricle
Apex of he a rt

A Infe rior he a rt borde r

Le ft common Bra chioce pha lic

ca rotid a rte ry a rte ry

Le ft s ubclavia n
a rte ry Arch of a orta

Le ft pulmona ry
a rte ry
S upe rior ve na cava
Le ft s upe rior Right pulmona ry
pulmona ry ve in a rte ry

Le ft infe rior Right s upe rior

pulmona ry ve in pulmona ry ve in

Right infe rior

Le ft a trium pulmona ry ve in
Right a trium
Corona ry Infe rior ve na
s ulcus cava

Le ft Corona ry
ve ntricle s inus

B Right ve ntricle Infe rior he a rt borde r

FIGURE 1-2. The heart and great vessels. A. The anterior view. B. The posterior aspect (or base), as viewed
from the back. (From Moore KL, Dalley AF, Agur AMR. Clinically Oriented Anatomy, 7th ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2014:137–138.)
4 Chapter 1

Ante rio r

Pulmonic
va lve

Aortic
va lve
FIGURE 1-3. The four heart valves
Tricus pid viewed from above with atria removed.
va lve The f gure depicts the period o
Mitra l ventricular f lling (diastole) during which
va lve the tricuspid and mitral valves are open
Annulus
and the semilunar valves (pulmonic and
fibros us
aortic) are closed. Each annulus f brosus
Annulus
surrounding the mitral and tricuspid
fibros us
valves is thicker than those surrounding
the pulmonic and aortic valves; all our
contribute to the heart’s f brous skeleton,
which is composed o dense connective
Po s te rio r tissue.

cardiac muscle cells, the histology o which is described later in the chapter. External to the
myocardium is a layer o connective tissue and adipose tissue through which pass the larger
blood vessels and nerves that supply the heart muscle. The epicardium is the outermost
layer o the heart and is identical to, and just another term or, the visceral pericardium
previously described.

Right Atrium and Ventricle

Opening into the right atrium are the superior and in erior venae cavae and the coronary
sinus (Fig. 1-4). The venae cavae return deoxygenated blood rom the systemic veins into the
right atrium, whereas the coronary sinus carries venous return rom the coronary arteries.
The interatrial septum orms the posteromedial wall o the right atrium and separates it rom
the le t atrium. The tricuspid valve is located in the f oor o the atrium and opens into the
right ventricle.
The right ventricle (see Fig. 1-4) is roughly triangular in shape, and its superior aspect
orms a cone-shaped outf ow tract, which leads to the pulmonary artery. Although the inner
wall o the outf ow tract is smooth, the rest o the ventricle is covered by a number o irregular
bridges (termed trabeculae carneae) that give the right ventricular wall a spongelike appear-
ance. A large trabecula that crosses the ventricular cavity is called the moderator band. It
carries a component o the right bundle branch o the conducting system to the ventricular
muscle.
The right ventricle contains three papillary muscles, which project into the chamber and
via their thin, stringlike chordae tendineae attach to the edges o the tricuspid valve leaf ets.
The leaf ets, in turn, are attached to the brous ring that supports the valve between the right
atrium and ventricle. Contraction o the papillary muscles prior to other regions o the ven-
tricle tightens the chordae tendineae, helping to align and restrain the leaf ets o the tricuspid
valve as they are orced closed. This action prevents blood rom regurgitating into the right
atrium during ventricular contraction.
At the apex o the right ventricular outf ow tract is the pulmonic valve, which leads to the
pulmonary artery. This valve consists o three cusps attached to a brous ring. During relax-
ation o the ventricle, elastic recoil o the pulmonary arteries orces blood back toward the
 Normal Cardiac Structure and Function 5

Pulmona ry a rte ry
Aorta
Pulmonic va lve

S upe rior ve na cava

Inte rve ntricula r s e ptum

Right a trium
Mode ra tor
ba nd

Tra be cula e
ca rne a e
Infe rior ve na cava

Corona ry s inus

Tricus pid va lve Right ve ntricle Pa pilla ry mus cle s

FIGURE 1-4. Interior structures of the right atrium and right ventricle. (Modif ed rom Goss CM. Gray’s
Anatomy. 29th ed. Philadelphia, PA: Lea & Febiger; 1973:547.)

heart, distending the valve cusps toward one another. This action closes the pulmonic valve
and prevents regurgitation o blood back into the right ventricle.

Left Atrium and Ventricle

Entering the posterior hal o the left atrium are the our pulmonary veins (Fig. 1-5). The
wall o the le t atrium is about 2 mm thick, being slightly greater than that o the right
atrium. The mitral valve opens into the le t ventricle through the in erior wall o the le t
atrium.
The cavity o the left ventricle is approximately cone shaped and longer than that o the
right ventricle. In a healthy adult heart, the wall thickness is 9 to 11 mm, roughly three times
that o the right ventricle. The aortic vestibule is a smooth-walled part o the le t ventricular
cavity located just in erior to the aortic valve. In erior to this region, most o the ventricle is
covered by trabeculae carneae, which are ner and more numerous than those in the right
ventricle.
The le t ventricular chamber (see Fig. 1-5B) contains two large papillary muscles. These
are larger than their counterparts in the right ventricle, and their chordae tendineae are thicker
but less numerous. The chordae tendineae o each papillary muscle distribute to both leaf ets
o the mitral valve. Similar to the case in the right ventricle, tensing o the chordae tendineae
during le t ventricular contraction helps restrain and align the mitral leaf ets, enabling them
to close properly and preventing the backward leakage o blood.
The aortic valve separates the le t ventricle rom the aorta. Surrounding the aortic valve
opening is a brous ring to which is attached the three cusps o the valve. Just above the
right and le t aortic valve cusps in the aortic wall are the origins o the right and le t coronary
arteries (see Fig. 1-5B).

Interventricular Septum
The interventricular septum is the thick wall between the le t and right ventricles. It is com-
posed o a muscular and a membranous part (see Fig. 1-5B). The margins o this septum
can be traced on the sur ace o the heart by ollowing the anterior and posterior interven-
tricular grooves. Owing to the greater hydrostatic pressure within the le t ventricle, the large
6 Chapter 1

Pulmona ry ve ins

Le ft a trium

Le ft a tria l
a ppe nda ge

Fibrous ring of
le ft AV orifice

Chorda e te ndine a e
Le ft ve ntricle
Pa pilla ry mus cle s

Ante rior cus p of mitra l va lve

To a ortic ve s tibule

Orifice of right corona ry a rte ry As ce nding a orta

Pos te rior cus p of a ortic va lve

Orifice of le ft
Pulmona ry a rte ry corona ry a rte ry
Le ft cus p of
Right a ortic s inus a ortic va lve
Right cus p of a ortic va lve

Inte rve ntricula r s e ptum,

me mbra nous pa rt

Chorda e te ndine a e
Inte rve ntricula r
s e ptum, mus cula r pa rt Ante rior cus p of mitra l va lve

Ante rior pa pilla ry mus cle

Right ve ntricle

Pos te rior
pa pilla ry mus cle

Tra be cula e ca rne a e

B
FIGURE 1-5. Interior structures of the left atrium and left ventricle. A. The le t atrium and le t ventricular (LV) in ow
region. B. Interior structures o the LV cavity. (Modif ed rom Moore KL, Dalley AF, Agur AMR. Clinically Oriented Anatomy,
7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2014:142–143.)
 Normal Cardiac Structure and Function 7

muscular portion o the septum bulges toward the right ventricle. The small, oval-shaped
membranous part o the septum is thin and located just in erior to the cusps o the aortic
valve.

To summarize the unctional anatomic points presented in this section, the ollowing is a
review o the path o blood f ow: deoxygenated blood is delivered to the heart through the
in erior and superior venae cavae, which enter into the right atrium. Flow continues through
the tricuspid valve ori ce into the right ventricle. Contraction o the right ventricle propels the
blood across the pulmonic valve to the pulmonary artery and lungs, where carbon dioxide is
released and oxygen is absorbed. The oxygen-rich blood returns to the heart through the pul-
monary veins to the le t atrium and then passes across the mitral valve into the le t ventricle.
Contraction o the le t ventricle pumps the oxygenated blood across the aortic valve into the
aorta, rom which it is distributed to all other tissues o the body.

Impulse-Conducting System
The impulse-conducting system (Fig. 1-6) consists o specialized cells that initiate the heart-
beat and electrically coordinate contractions o the heart chambers. The sinoatrial (SA) node
is a small mass o specialized cardiac muscle bers in the wall o the right atrium. It is located
to the right o the superior vena cava entrance and normally initiates the electrical impulse
or contraction. The atrioventricular (AV) node lies beneath the endocardium in the in ero-
posterior part o the interatrial septum.
Distal to the AV node is the bundle of His, which per orates the interventricular septum
posteriorly. Within the septum, the bundle o His bi urcates into a compact, cablelike struc-
ture on the right side, known as the right bundle branch, and a broad sheet o bers that
continues over the le t side o the septum, the left bundle branch.
The right bundle branch is thick and deeply buried in the muscle o the interventricular
septum and continues toward the apex. Near the junction o the interventricular septum
and the anterior wall o the right ventricle, the right bundle branch becomes subendocardial

S inoa tria l node

Mitra l va lve

Me mbra nous pa rt of
Corona ry s inus IV s e ptum

Bifurca tion of bundle

of His
Atriove ntricula r node Mus cula r pa rt of
IV s e ptum
Bundle of His
Le ft bundle bra nch

Right bundle bra nch Purkinje fibe rs unde r

e ndoca rdium of pa pilla ry
mus cle
Mode ra tor ba nd

FIGURE 1-6. Main components of the cardiac conduction system. This system includes the sinoatrial node,
atrioventricular node, bundle o His, right and le t bundle branches, and the Purkinje f bers. The moderator
band carries a large portion o the right bundle. (IV, interventricular).
8 Chapter 1

and bi urcates. One branch travels across the right ventricular cavity in the moderator band,
whereas the other continues toward the tip o the ventricle. These branches eventually arbo-
rize into a nely divided anastomosing plexus that travels throughout the right ventricle.
Functionally, the le t bundle branch is divided into an anterior and a posterior ascicle and
a small branch to the septum. The anterior ascicle runs anteriorly toward the apex, orming a
subendocardial plexus in the area o the anterior papillary muscle. The posterior ascicle trav-
els to the area o the posterior papillary muscle; it then divides into a subendocardial plexus
and spreads to the rest o the le t ventricle.
The subendocardial plexuses o both ventricles send distributing Purkinje bers to the
ventricular muscle. Impulses within the His–Purkinje system are transmitted rst to the papil-
lary muscles and then throughout the walls o the ventricles, allowing papillary muscle con-
traction to precede that o the ventricles. This coordination prevents regurgitation o blood
f ow through the AV valves, as discussed earlier.

Cardiac Innervation
The heart is innervated by both parasympathetic and sympathetic a erent and e erent
nerves. Preganglionic sympathetic neurons, with cell bodies located within the upper ve
to six thoracic levels o the spinal cord, synapse with second-order neurons in the cervical
sympathetic ganglia. Traveling within the cardiac nerves, these bers terminate in the heart
and great vessels. Preganglionic parasympathetic bers originate in the dorsal motor nucleus
o the medulla and pass as branches o the vagus nerve to the heart and great vessels. Here,
the bers synapse with second-order neurons located in ganglia within these structures. A
rich supply o vagal a erents rom the in erior and posterior aspects o the ventricles mediates
important cardiac ref exes, whereas the abundant vagal e erent bers to the SA and AV nodes
are active in modulating electrical impulse initiation and conduction.

Cardiac Vessels
The cardiac vessels consist o the coronary arteries and veins and the lymphatics. The largest
components o these structures lie within the loose connective tissue in the epicardial at.

Coronary Arteries
The heart muscle is supplied with oxygen and nutrients by the right and le t coronary arter-
ies, which arise rom the root o the aorta just above the aortic valve cusps (Fig. 1-7; see also
Fig. 1-5B). A ter their origin, these vessels pass anteriorly, one on each side o the pulmonary
artery (see Fig. 1-7).
The large le t main coronary artery passes between the le t atrium and the pulmonary
trunk to reach the AV groove. There it divides into the le t anterior descending (LAD) coro-
nary artery and the circumf ex artery. The LAD travels within the anterior interventricular
groove toward the cardiac apex. During its descent on the anterior sur ace, the LAD gives o
septal branches that supply the anterior two thirds o the interventricular septum and the
apical portion o the anterior papillary muscle. The LAD also gives o diagonal branches that
supply the anterior sur ace o the le t ventricle. The circumf ex artery continues within the
le t AV groove and passes around the le t border o the heart to reach the posterior sur ace. It
gives o large obtuse marginal branches that supply the lateral and posterior wall o the le t
ventricle.
The right coronary artery (RCA) travels in the right AV groove, passing posteriorly
between the right atrium and ventricle. It supplies blood to the right ventricle via acute
marginal branches. In most people, the distal RCA gives rise to a large branch, the posterior
descending artery (see Fig. 1-7C). This vessel travels rom the in eroposterior aspect o the