HISTOLOGY OF THE CARDIOVASCULAR SYSTEM

HISTOLOGY OF THE CARDIOVASCULAR SYSTEM

Peter B. Baker, M.D.

e-mail: Peter.Baker@nationwidechildrens.orgReference source for eLearning, Histology-Cardiac, Week 1, April 1, 2014Page References - Leslie P. Gartner and James L. Hiatt. Color Textbook of Histology, 3rd Edition, WB Saunders, 2007I.HEART

A. Atrial and ventricular anatomy

1. Right atrium receives systemic venous return through superior and inferior vena cava, coronary sinus: fossa ovalis (foramen ovale), atrial appendage.

2. Right ventricle thin wall (0.3 cm thick), coarse apical trabeculations, supraventricular crest separates inflow from outflow tract, membranous ventricular septum behind the junction of the septal and anterior tricuspid valve leaflets, prominent muscle bundles include moderator band and septomarginal trabeculation.

3. Left atrium receives pulmonary venous return: flap valve of the foramen ovale, tubular atrial appendage.

4. Left ventricle thick wall (1 1.5 cm), anterior mitral valve leaflet separates the inflow and outflow tracts.

B.Myocardium (refer to pp 160-167, 175-179 and 267-269)There are no well-defined layers in the ventricular myocardium. Muscle bundles are composed of parallel myocytes. Myocytes are also called cardiomyocytes and muscle fibers. The myocardium consists of myocytes, collagen, blood vessels, adipose tissue (more in the right ventricle than the left ventricle) and nerves. Each myocyte is surrounded by basement membrane composed of collagen and laminin. The cell membrane is called the sarcolemma. Myocytes have one or two centrally located nuclei and the cytoplasm has a striated appearance due to the contractile proteins (described below). Although myocytes appear to be arranged end-to-end, there is considerable branching which produces a complex arrangement of interconnection. Cardiac myocytes are approximately 85 to 100 microns in length and 15 to 18 microns in diameter.

Ultrastructure of the Myocardium

Cardiac myocytes and skeletal muscle cells share many ultrastructural

features.

1.Contractile structures

The contractile proteins are organized into well-defined, parallel units

called myofibrils. Each myofibril contains a number of proteins including

thin filaments (actin) and thick filaments (myosin). These two filaments,

called myofilaments, are arranged in highly organized repetitive units

called sarcomeres. Refer to figures 8-4 on page 161 and 8-5 on page 162 as

well as Musculoskeletal Block and be sure you can identify the Z disk (band), I band, A band, H band and M line. Note that each myosin filament is surrounded by 6 actin filaments where the two filaments overlap. There are a few important points about the structure and composition of the myofibrils.

a.One sarcomere is the structure between two consecutive Z disks.

b.The A band is the length of the myosin filaments and the actin

filaments run from the Z disk to the edge of the H band.

c.The thin filaments, in addition to actin, contain troponin I, C and T as

well as tropomyosin. Nebulin extends along the length of actin and acts as a

template to regulate the thin filament length. Alpha actinin is a Z disk protein

that binds the thin filaments in parallel arrays.d.Titin is a protein attached to the thick filaments and extends from the Z disk to the M line. Titin maintains the central position of the thick filaments in the sarcomere.

e.Creatine kinase which catalyzes the formation of ATP from ADP, is a

major component of the H band.

f.Details of the mechanism involved in muscle contraction are beyond the scope of this lecture. Calcium binding to troponin C activates a conformational change which causes actin filaments to slide along myosin filaments. The sliding movement is dependent on ATP.

g.During contraction the A band width does not change. The I band

width is greater during relaxation and narrower during contraction.

2.Transverse (T) Tubules

T tubules are invaginations of the cell membrane (sarcolemma) into the

cytoplasm along the Z disks. Each T tubule is in close contact

with a sarcoplasmic reticulum tubule. The site of contact is called a dyad.

Notethat in skeletal muscle the T tubules are in close contact with two

sarcoplasmic reticulum tubules, called a triad. When the action potential

reaches a myocardial cell, calcium initially enters the cytoplasm through

calcium channels in the sarcolemma and T tubules. This triggers a

greater release of calcium from the sarcoplasmic reticulum tubules.

3.Sarcoplasmic reticulum

This specialized smooth endoplasmic reticulum stores calcium during relaxation and releases calcium into the cytoplasm to induce contraction.

4.Other cytoplasmic elements

Mitochondria, glycogen, intermediate filaments (desmin and vimentin),

lipid and lipofuscin (found adjacent to the nucleus and increases with

increasing age).

5.Intercalated disks

Specialized junctional complexes (intercalated disks) join myocytes end-

to-end and side-to side. They have a stepwise configuration. Segments

perpendicular to the long axis join myocytes end-to-end and have desmosomes

(providing mechanical attachment) and fasciae adherentes (the attachment sites for actin filaments in the last sarcomere). The segments of intercalated disks oriented parallel to the myocytes contain gap junctions. These junctions are sites of ionic communication between cells and provide for synchronous muscle contraction.

6.Atrial cytoplasmic granules

Atrial myocytes, predominantly in atrial appendages, have cytoplasmic

dense granules which contain atrial natriuretic peptide (ANP). When the

atria are distended this polypeptide is released. ANP causes diuresis

(increased urine output) by increasing glomerular filtration rate in the

kidneys, increasing sodium and water excretion and antagonizing the

action of angiotensin II and renin.

7. Differences between skeletal and cardiac muscle

Cardiac Skeletal

Central, single nucleus Peripheral, multiple nuclei T tubules at level of Z disks T tubules at A-I junction

Intercalated disks No intercalated disks

T tubule SR junction, dyad T tubule SR junction, triad

Cytoplasmic granules with ANP (atria) No granules

Fewer SR tubules

More mitochondria with more cristae

C.Endocardium (pp 267-268)

This is the inner lining of all the heart chambers and consists of an

endothelial lining and subendothelial collagen and elastic fibers.

D.Visceral pericardium (p 269)

The surface of the heart is covered by a simple layer of mesothelial cells

with a thin underlying layer of collagen.

E.Epicardium (p 269)

This is the connective tissue between the visceral pericardium and the

myocardium. The epicardium contains collagen, adipose tissue, blood

vessels and nerves.

F. Anatomy of the cardiac valves

1. Arterial valves (pulmonary and aortic) Three semilunar leaflets, adjacent leaflets are completely separate from each other at the commissures. Sinus of Valsalva is a pocket in the root of the aorta or pulmonary artery behind each leaflet.

2. Tricuspid valve Anterior, posterior and septal leaflets are anchored to papillary muscles and the ventricular wall by chordae tendineae. The leaflets attach to the wall along a circular annulus. There is no fibrous continuity between the tricuspid and pulmonary valves.

3. Mitral valve Anterior and posterior leaflets are anchored to anterior and posterior papillary muscles by chordae tendineae and the leaflets are attached to the wall along a circular annulus. Few chordae also attach to the ventricular wall; however, none attach to the ventricular septum. The commissures are arranged with one posterior and medial and the second anterior and lateral. There is fibrous continuity between the anterior leaflet and the aortic valve. The anterior leaflet divides the inflow from the outflow tract in the left ventricle.

G.Cardiac valves

The tricuspid and mitral valves have 4 identifiable histologic layers. They

are listed in order from the atrial surface to the ventricular surface.

1.Atrialis a thin layer of dense collagen.

2.Spongiosa a thin, irregular layer of loose collagen with proteoglycans.

3.Fibrosa dense collagen forming most of the cross-sectional area of the

leaflet and providing tensile strength.

4.Ventricularis a thin, poorly demarcated layer of dense collagen.

5. Chordae tendineae have a dense central core of collagen and a peripheral thin layer of elastic fibers.

The pulmonary and aortic valves have similar layers as described above.

H.Conduction system (p 268)

The specialized conduction system consists of the sinoatrial (SA) node,

atrioventricular (AV) node, bundle of His and bundle branches composed of

Purkinje cells.

The muscle cells of the SA node, AV node and bundle of His are smaller

and contain fewer myofibrils compared with the contractile myocytes. The

Purkinje cells of the bundle branches are larger but contain fewer myofibrils and more glycogen than the contractile myocytes.

1.SA node is located in the subepicardial area at the junction of the right

atrial appendage with the superior vena cava. There are no

morphologically recognizable specialized conduction bundles between

the SA node and the AV node.

2.AV node is located in a subendocardial location just above the septal

leaflet of the tricuspid valve. This node gives rise to a bundle which

courses anteriorly through the central fibrous body and is called the

bundle of His. The distal aspect of the His bundle gives rise to left and

right bundle branches, which course along the subendocardial area of the interventricular septum (right and left sides) until merging with contractile

myocardium.

II.VASCULAR (CIRCULATORY) SYSTEM (pp 251 - 271)

A.Arteries Arteries have 3 clearly identifiable layers or tunics: intima (inner layer),

media and adventitia (outer layer). In all arteries, the intima is composed of

an endothelial lining and subendothelial collagen. Larger muscular arteries and

elastic arteries may have a few smooth muscle cells and macrophages in the

intima. The adventitia is composed of collagen and a few elastic fibers. The

elastic arteries have small vessels in the adventitia and outer media called the

vasa vasorum. These vessels provide oxygen and nutrients to the outer layers of

the arteries. The inner layers of large arteries and the entire wall of smaller

arteries receive oxygen and nutrients directly from the vessel lumen. The

structure of the media varies in different arteries as described below.

1.Elastic arteries

These arteries do not contract but absorb the systolic pulse wave by

distending and they maintain diastolic pressure by elastic recoil. Elastic

arteries have a poorly defined internal elastic layer between the intima

and media. The media has concentric elastic lamellae with interspersed

smoothmuscle cells, collagen and proteoglycans. There is no external

elastic layer. The largest arteries (aorta, pulmonary artery,

brachiocephalic artery, common carotid arteries, subclavian arteries and

common iliac arteries) are elastic arteries.

2.Muscular arteries

There is a gradual transition from elastic arteries to muscular arteries.

Muscular arteries range from fairly large caliber vessels to small vessels

measuring only 150 (m in diameter. Muscular arteries can contract and

have a role in controlling blood distribution to various organs. The intima

and media are separated by a prominent internal elastic layer. The

media is composed of spirally arranged smooth muscle cells, few elastic

fibers and sparse collagen. The media and adventitia are separated by

an external elastic layer.

3.Arterioles

Arterioles regulate blood flow to different capillary beds by dilating andconstricting. Precapillary sphincters are located between arterioles and capillaries and control blood flow into capillary beds. Partial contraction (or tone) of arteriole smooth muscle can help regulate blood flow and generalized increase or decrease in tone can increase or decrease blood pressure. Arterioles are 20 to 130 (m in diameter. They have a thin internal elastic layer and no external elastic layer. The media is formed by one to several layers of smooth muscle cells and the adventitia is thin. Under certain conditions (i.e. hypertension, diabetes mellitus) plasma proteins accumulate in the media called hyalinization or hyaline arteriolosclerosis. In some tissues, arterioles give rise to metarterioles which have a discontinuous smooth muscle media.

B.CapillariesGas and nutrient exchange occurs at the level of the capillaries. These

vessels have very thin walls composed of endothelial cells surrounded by a

basement membrane. Pericytes are located along the outside of the capillaries. The diameter is 5-10 (m. Since red blood cells are 7(m in diameter, they must deform to pass through the smallest capillaries. The term microvasculature refers to terminal arterioles or metarterioles, capillaries and post capillary venules. Slightly larger capillaries (preferential or thoroughfare channels) have continuous flow and smaller (true) capillaries have intermittent flow regulated by precapillary sphincters. With decreased oxygen/nutrient requirements the precapillary sphincters close and blood is routed through thoroughfare channels. Some vascular beds have arteriovenous connections (through channels) connecting terminal arterioles with postcapillary venules and bypassing the capillary bed. There are three types of capillaries based on the endothelial morphology.

1.Continuous capillary

The endothelial cells form a complete, continuous lining. Tight junctions

are formed at points of cell to cell contact. The basement membrane is

also continuous. Exchange occurs by diffusion (of gases) and through

pinocytotic vesicles (or caveolae). Bidirectional transport of substances

is called transcytosis. These capillaries are found in muscle, brain, bone,

lung and other tissues.

2.Fenestrated capillary

The endothelial cells have pores or fenestrae (holes through the cell)

which are 10 to 100 nm in diameter. Some fenestrae are completely

open and some have a thin diaphragm. The basement membrane is

continuous and forms an important diffusion barrier over the fenestrae.

These capillaries are present in sites of higher fluid transport such as

glomeruli and intestine.

3.Discontinuous (sinusoidal) capillary

There are gaps between endothelial cells and larger fenestrae through

individual cells. The basement membrane is discontinuous. These

capillaries are found in sinusoidal tissues where free exchange between

blood and the parenchyma is needed such as liver and spleen.

C.VeinsPostcapillary venules are structurally similar to capillaries. They have a wider lumen and are the preferred sites for migration of leukocytes into tissue (called diapedesis). Muscular venules connect the postcapillary venules with larger veins. Veins have thinner walls and are more distensible compared with arteries of the same size. A small increase in luminal hydrostatic pressure in veins may significantly increase blood volume. This can lead to pooling, congestion and stasis.

Veins have layers similar to arteries; however, distinction between layers isless

clear. There is no internal or external elastic lamina. The media is thinner and the

smooth muscle cells have irregular (roughly circular) orientation. In some veins

there is a single media/adventitial layer. Venous valves are projections of intima. The valves have a thin central core of collagen and elastic fibers covered by endothelium. The valves prevent retrograde blood flow.

D.Lymphatic vessels (p 270-271)

The lymphatic system begins as blind-end capillaries. These vessels have

an endothelial lining lacking tight junctions and lacking a complete

basement membrane. At some points the endothelial cells are directly

anchored to adjacent connective tissue by filaments. Tissue fluid along with

albumin and large molecules enter the capillaries. The capillaries drain into

larger lymphatic vessels, eventually leading to the thoracic duct or right

lymphatic duct. Larger lymphatic vessels have three layers in the wall,

similar to small veins. Valves are present as seen in veins. Lymph nodes

are located along the pathway of lymphatic vessels. Fluid is pushed

through lymphatics by intrinsic muscular contraction (triggered when a

segment becomes distended), contraction of adjacent skeletal muscle,

arterial pulsation and compression from outside the body. No lymphatic

vessels are present in cartilage, bone, central nervous system, bone

marrow or surface epithelium.

E.Specialized capillary bedsMost capillary beds are between arterioles and venules. However, there are exceptions. The renal glomerulus is an arterial portal system. Blood enters the glomerular capillaries through an afferent arteriole and exits via an efferent arteriole. The efferent arteriole then gives rise to another capillary bed, the vasa

recta, which surrounds renal tubules (loops of Henle). Capillaries in the

liver represent a portal venous system. Intestinal tract capillaries drain into the

portal vein. The portal vein leads to sinusoidal capillaries in the liver which then

drain into hepatic veins. A similar portal venous system exists in the pituitary.

Capillaries of the hypothalamus drain via veins in the pituitary stock which then

give rise to a capillary bed in the anterior pituitary. PAGE 3