INTRODUCTION

The heart is a four-chambered organ responsible for pumping

Issues of Concern
The cells that constitute the heart are unique. It can initiate and
propagate electricity throughout each cardiac cell. This physiology
allows the heart to contract synchronously, permitting for optimal
function of circulating blood to the lungs and the rest of the distal
organs.
 STRUCTURE
The fibrous skeleton, cardiac muscle, and impulse conduction system
constitute the basic framework of the heart. The base of the heart
contains a highly dense structure known as the fibrous or cardiac
skeleton. Functions of the fibrous skeleton include providing as a
strong framework for cardiomyocytes, anchoring the valvular leaflets,
and acting as electrical insulation separating the conduction in the
atria and ventricles. The wall of the heart separates into the following
layers: epicardium, myocardium, and endocardium. These three layers
of the heart are embryologically equivalent to the three layers of
blood vessels: tunica adventitia, tunica media, and tunica intima,
respectively. A double-layer, fluid-filled sac known as the
pericardium, surrounds the heart. The two layers of the pericardium
are called the outer fibrous/parietal pericardium and the inner
serous/visceral pericardium. The epicardium constitutes the visceral
pericardium, underlying fibro-elastic connective tissue, and adipose
tissue.Coronary arteries and veins, lymphatic vessels and nerves run
below the epicardium. The endocardium is composed of the
endothelium and the subendothelial connective tissue layer. The
subendocardium is found between the endocardium and myocardium
and contains the impulse-conducting system.
The impulse conducting system has specialized cardiac cells for the
conduction of electrical impulses throughout the heart. Electrical
impulses initiate at the sinoatrial (SA) node, situated at the junction of
the superior vena cava and right atrium. These impulses travel
throughout the atria until it reaches the atrioventricular (AV) node;
located between the interatrial and interventricular septum. As the
fibers travel inferiorly, it penetrates the central fibrous body of the
cardiac skeleton to form the bundle of His. These fibers are the
Purkinje fibers after they divide within the interventricular septum
and branch into the ventricles.
Valves are an important component of the heart. Not only do they act
as an exit gate, but they also prevent backflow into the chamber. The
aortic valve, separating the aorta from the left ventricle, and the
pulmonic valve, separating the pulmonary artery from the right
ventricle, are known as semilunar valves. The two atrioventricular
(AV) valves are the tricuspid and mitral valves. The tricuspid valve
marks the separation between the right atrium and right ventricle
while the mitral valve separates the left atrium from the left ventricle.
A unique aspect of the AV valves is their attachments to the ventricles
with the assistance of chordae tendinae inserting onto the papillary
muscle of the ventricles.

FUNCTION
The heart's main function is to pump blood throughout the body.
Cardiac function can be best represented by cardiac output, the
amount of blood pumped out of the heart per minute. Many factors
determine the cardiac output. The product of stroke volume and heart
rate equals cardiac output. Hence, cardiac output is directly alterable
through variations in these two factors. Stroke volume is the blood
volume ejected after ventricular contraction, calculated by taking the
difference between end-diastolic volume and end-systolic volume.
Contractility, afterload, and preload can change stroke volume.
Preload is the amount of stress placed on cardiomyocytes by the end-
diastolic volume before systole. The end-diastolic volume is the best
way to measure preload. On the other hand, afterload is the total
tension exerted onto the ventricle that must overcome during systole.
The law of LaPlace is the foundation for the definition of afterload.
Therefore, changes in pressure, radius, or wall thickness directly
affect afterload.
 TISSUE PREPARATION
Histological and cytological studies of the heart are necessary for
diagnostic purposes, assessment of allograft rejection after a cardiac
transplant, or evaluation of the effect of drug toxicity on the heart. An
endomyocardial biopsy obtains cardiac tissue to be analyzed.
During an endomyocardial biopsy procedure, 1 to 2 mm3 of
endocardium and myocardium is taken from the right
ventricle Peripheral proximity to the venous entry of the bioptome
and a thicker wall, relative to the atrium, makes the right ventricle an
ideal location for a biopsy. The cardiac sample is then placed into a
fixative, such as formalin, to preserve the tissue. These preserved
samples are then placed into cassettes, embedded in paraffin wax,
thinly sliced and mounted onto glass slides. Hematoxylin and eosin is
an initial, basic stain for visualization of the heart tissue under light
microscopy.
 HISTOCHEMISTRY AND CYTOCHEMISTRY
The study of cells and tissue (histochemistry) and intracellular
activities (cytochemistry) is useful for narrowing down the correct
diagnosis. Immunohistochemistry uses antibodies to target specific
antigens in a specimen. The antibody-antigen complex can then be
stained to appreciate the presence of the particular antigen. This test
can aid in the diagnosis of acute allograft rejection, amyloidosis,
neoplasms, and cardiomyopathy.[5] T-lymphocytes, seen in
myocarditis, can also be identified with the help of
immunohistochemistry. Immunofluorescence is very similar to
immunohistochemistry. However, the antibodies contain a fluorescent
dye which are visible when the antibody is attached to an antigen.
Immunofluorescence can assist with the diagnosis of allograft
rejection and certain cardiomyopathies.[7]
.
 Microscopy Light
Histologically, the heart is mainly composed of cardiomyocytes and
connective tissue. Dense connective tissue with elastic fibers is
present in the cardiac/fibrous skeleton. Certain stains such as the
Masson's elastic trichrome stains can help visualize these components.
The pericardium subdivides into two layers, a superficial fibrous
layer, and deeper serous layer. The fibrous layer is composed of
fibrous connective tissue. The serous layer further divides into two
layers, an outer layer inseparable from the fibrous pericardium and an
inner layer overlying the myocardium. Both of these layers are
histologically the same; composed of a continuous layer of
mesothelial cells with microvilli facing the pericardial cavity. The
fibrous pericardium and the outer serous pericardium combined is
known as the parietal pericardium. The inner serous pericardium,
known as the visceral pericardium, is also part of the epicardium. In
between the outer and inner serous layer is a potential space known as
the pericardial cavity containing pericardial fluid, which is produced
and reabsorbed by the microvilli on the mesothelial cells.
A large part of the cardiac wall is made up of the myocardium.
Cardiomyocytes join together to make up this layer. These
cardiomyocytes are striated like myocytes found in skeletal muscle.
However, unlike skeletal muscle cells, they are branched, contain
intercalated disks, and are usually mononucleated. They are also
unable to regenerate. After an insult, such as a myocardial infarction,
the necrotic area gets replaced by scar tissue. This histological change
is evident under light microscopy as the fibrous component of the scar
tissue is stained blue with Masson's elastic trichrome stain.
The endocardium consists of a single layer of endothelial cells lining
the chambers of the heart. Occasionally, small amounts of smooth
muscle can also be in the endocardium. Compared to the right atrium,
the left atrium has a thicker endocardium because of high pressure
from the pulmonary veins. The subendothelial layer, between the
myocardium and endocardium, contain loose elastic tissue, collagen
bundles, nerves and occasionally blood vessel.
The conduction system consists of specialized myocardial cells and
fibers that allow for the initiation and propagation of impulses. The
SA node is composed of nodal (P) cells and transitional (T) cells.
These cells are looks similar to myocardial cells but contain fewer
myofibrils. Dense connective tissue insulates and separates this area
from the rest of the atria. The atrioventricular (AV) node, situated
next to the fibrous skeleton of the heart, has specialized muscle fibers
that receive impulses from the SA node. Purkinje fibers, branches
from the atrioventricular nodes, can be located within the epicardium.
These fibers are rich in glycogen and also contain fewer myofibrils.
Valves have three layers: spongiosa, fibrosa, ventricularis. Identifying
these layers can help orient the valves on microscopy. The spongiosa
is on the atrial side of atrioventricular valves or arterial side of
semilunar valves. Large amounts of proteoglycans, such as
glycosaminoglycan, and loose connective tissue, are characteristic of
the spongiosa layer.]
 Pathophysiology
In hypertrophic cardiomyopathy, changes at the cellular level have a
significant impact on the gross structure and physiology of the heart.
There are several causes for hypertrophic cardiomyopathy. Some
examples include genetic mutation, hypertension, and aortic stenosis.
Key histologic findings are cardiomyocyte disarray (hypertrophied
and disorganized myocytes), and interstitial fibrosis of the left
ventricle and interventricular septum.[11] These cellular changes can
be due to increased afterload placed on the left ventricle or mutations
in sarcomere proteins, such as the B-myosin heavy chain (MYH7) and
the cardiac myosin binding protein C (MYBPC3) genes.[12] Under
electron microscopy, abnormal myocyte and sarcomeres are visible in
areas of myocyte disarray. Masson's elastic trichrome stain can help
identify areas of fibrosis. Further hypertrophy of the myocardium
causes diastolic dysfunction and heart failure.
 Clinical Significance
A variety of pathologies can affect every area of the heart. The fibrous
skeleton is near the cardiac valves and conduction fibers. During a
valvectomy, portions of the fibrous skeleton may undergo accidental
removal. Complications, such as arrhythmias, can occur if the
conduction fibers are damaged.
Constrictive pericarditis and cardiac tamponade are two serious
pathologies involving the pericardium. Occasionally, a
pericardiectomy is needed to allow for the heart to function
seamlessly. The pericardium is now a specimen that must undergo
evaluation. Fibrosis and chronic inflammation present in constrictive
pericarditis. Granulomatous infection and metastasis are not common
but must be ruled out. Epicardial fat can be an incidental finding in
these specimens.
The myocardium occupies the bulk of the heart. Restrictive
cardiomyopathy, viral myocarditis, cardiac allograft rejection can
have uncommon histological findings. In restrictive cardiomyopathy,
the histology depends on the underlying etiology. Some examples of
causes of restrictive cardiomyopathy include sarcoidosis, amyloidosis,
iron-overload cardiomyopathy, and neoplasms. In viral myocarditis,
the virus causes lymphocytes to infiltrate the myocardium, and
infected cardiomyocytes undergo necrosis. Shortly after the cardiac
transplant, cardiac allograft rejection may occur and must be
diagnosed with an endomyocardial biopsy. Findings include abnormal
myocytes and the presence of lymphocytes
Aging can cause significant changes to the valves and conduction
system. Increased collagen fibers and calcification results in valvular
abnormalities. An example of valvular changes in the elderly is aortic
stenosis. If the valve is not replaced, severe aortic stenosis can cause
syncope, angina, and eventually, death. Fibrosis of the SA node and
bundle branch is also a result of aging. Consequently, patients can
develop a left bundle branch block or other related arrhythmias.