LECTURE № 1. «CARDIOVASCULAR DISEASES: ATHEROSCLEROSIS.
ARTERIAL HYPERTENSION. ISCHEMIC HEART DISEASE»
Arteriosclerosis (“hardening of the arteries”) is a generic term for thickening
and loss of elasticity of arterial walls. It occurs in three forms:
1)Atherosclerosis – most frequent and important pattern.
2)Mцnckeberg medial calcific sclerosis – characterized by calcific deposits in
muscular arteries.
3)Arteriolosclerosis – diasease of small arteries and arterioles, most often associated
with hypertension and diabetes mellitus.
Atherosclerosis (ATH) is thickening of the artery resulting from deposition of
specific atheromatous lesions.
Global in distribution, ATH overwhelmingly contributes to more mortality –
approximately half of all death – and serious morbidity in the Western World than any
other disorder.
ATH primarily affects elastic arteries (e.g. aorta, carotid and iliac arteries) and large
and medium-sized muscular arteries (e.g. coronary, popliteal arteries). Symptomatic
atherosclerotic disease most often involves the arteries supplying the heart, brain,
kidneys and lower extremities.
Etiology. The basic abnormality in ATH is the deposition of complex lipids in the
intima. The cause is uncertain. Numerous risk factors have been identified:
1)increasing age – some degree of ATH is present after age 30 years,
2)obesity,
3)lack of physical exercise,
4)male sex – males are affected more than females,
5)hyperlipidemia – is the major risk factor, especially – hypercholesterolemia or
increased level of low-density lipoprotein – cholesterol,
6)hypertension,
7)cigarette smoking,
8)diabetes mellitus.
Pathogenesis. Modern conception considers ATH to be a chronic inflammatory
response of the arterial wall initiated by injury to the endothelium. Central to this thesis
are the following:
1)Chronic endothelial injury, usually subtle, with resultant endothelial dysfunction,
yielding increased permeability, leukocyte adhesion and thrombotic potential.
2)Insudation of lipoproteins into the vessel wall.
3)Adhesion of blood monocytes and other leukocytes to the endothelium, followed by
their migration into the intima and their transformation into macrophages and foam
cells.
4)Adhesions of platelets.
5)Release of factors from activated platelets, macrophages or vascular cells that cause
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migration of SMCs from media into the intima.
6)Proliferation of CMCs in the intima and elaboration of extracellular matrix, leading to
accumulation of collagen and proteoglycans.
7)Enhanced accumulation of lipids both within cells (macrophages and SMCs) and
extracellularly.
Morphology.
There are 3 stages of ATH:
1.Fatty streaks – composed of lipid-filled foam cells, are not significantly raised and
thusdo not cause any disturbances in blood flow. They begin as multiple yellow, flat
spots (fatty dots) less than 1 mm in diameter that coalesce into elongated streaks, 1 cm
or longer. Fatty streaks appear in aortas of some children younger than 10 year of age.
They increase in number until about age 20 years and than remain static or decrease.
The relationship of fatty streaks to atherosclerotic plaques is uncertain: although they
May evolve into precursors of plaques, not all fatty streaks are destined to become
advanced atherosclerotic lesions.
2.Fibrous atheromatous plaque (also called fibrofatty or fibrolipid plaque; atheroma).
This is a basic lesion of clinical ATH. The plaque appears grossly as a yellow-white
elevation on the intimal surface of the artery. When cut across, the center of a plaque
consist of soft, yellow, grumous material (greek word “athere” = porridge or gruel).
They vary in size from 0.3 to 1.5 cm in diameter but sometimes coalesce to form
larger masses. Atherosclerotic lesions usually involve the arterial wall only partially
and are patchy and variable along the vessel length. Focal and sparsely distributed at
first, atherosclerotic lesions become more and more numerous and diffuse as the
disease advances.
In the characteristic distribution of atherosclerotic plaques, the abdominal aorta is
usually much more involved than is the thoracic aorta, and lesions tend to be much
more prominent around the origins (ostia) of major branches. The most intensively
involved vessels are the coronary arteries, the popliteal arteries and the internal carotid
arterias. Vessels of upper extremities are usually spared, as are the mesenteric and
renal arteries, except at their ostia.
Atherosclerotic plaques have three principal components:
1)Cells, including SMCs, macrophages and other leukocytes.
2)Extracellular matrix, including collagen, elastic fibers and proteoglycans.
3)Intracellular and extracellular lipid.
Microscopically, there are three zones:
1)Fibrous cap – under the endothelium, consisting of dense collagen, SMCs,
macrophages.
2)Necrotic center – which consist of foam cells (lipid-laden macrophages and SMCs),
extracellular lipid – cholesterol crystals and cell debris.
3)Basal zone – composed of proliferated SMCs and connective tissue.
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Different plaques contain varying amounts of these three layers; some are mainly
fibrous, and others predominantly fatty. Particularly around the periphery of the
lesions, there is usually evidence of neovascularization (proliferating small blood
vessels). Plaques generally continue to change and progressively enlarge through cell
death and degeneration, synthesis and degradation of extracellular matrix. Moreover
plaques often undergo calcification.
3.Complicated plaque.
1)Ulceration of the endothelium overlying the plaque may cause the lipid contents of
the plaque to be discharged into the circulation as cholesterol emboli.
2)Thrombosis is the most important complication of ATH: is caused by slowing and
turbulence of blood in the artery in the region of the plaque and ulceration of the
plaque. Thrombosis may cause partial or complete occlusion of the artery and
thromboembolism.
3)Hemorrhage into a plaque may occur initiated by rupture of either the overlying
fibrous cap or the thin-walled capillaries the vascularize the plaque. Moreover,
ulceration of plaque may lead to rupture of vessel wall and internal hemorrhage.
For example, rupture of aorta complicated with hemoperitoneum and rupture of
cerebral arteries lead to hematoma of brain.
4)Aneurisms. The arterial wall may be weakned to an extent that leads to dilation or
aneurism formation. Atherosclerotic aneurisms, occur mainly in the abdominal
aorta and appear as a fusiform dilation of the whole vessel circumference or
succular bulge on one side of it.
Clinical effects of ATH related to the major arteries involved
Arteries involved
Coronary arteries
Cerebral arteries
Iliofemoral arteries
Celiac and
mesenterial arteries
Renal arteries
Aorta
Clinical effect
Due to acute ischemia
Due to chronic ischemia
Sudden cardiac death
Chronic ischemic heart disease
Myocardial infarction
Cerebral infarction
Senile dementia
(atrophy of cerebral cortex in
old age)
Gangrene
Intermittent claudication
(disfunction of lower extremities
due to atrophy of skeletal
muscles)
Intestinal infarction and gangrene ---------------------------Renal infarction
Renovascular hypertension
Nephrosclerosis
Aneurism → Rupture → Hemorrhage
Mural thrombosis → Thromboembolism → Infarctions of inner
organs
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ARTERIAL HYPERTENSION
Elevated blood pressure (hypertension) affects both the function and the structure
of blood vessels. Although hypertension is a common health problem with
asymptomatic until late in its course. It is one of the most important risk factors in both
coronary heart disease and cerebrovascular accidents.
Ninety percent to 95% of hypertension is idiopathic (essential hypertension),
which is compatible with long life. This type of hypertension is a complex
multifactorial disorder.
Secondary hypertension may be: 1)renal, 2)endocrine, 3)cardiovascular,
4)neurologic.
Hypertensive Vascular Disease
Morphology. Hypertension is associated with two forms of small blood vessel
disease: hyaline arteriolosclerosis and hyperplastic arteriolosclerosis.
Hyaline arteriolosclerosis. This vascular lesion consist of a homogenous, pink
hyaline thickning of the walls of arterioles with loss of underlying structural detail and
with narrowing of the lumen. The lesions reflect leakage of plasma components across
vascular endothelium and excessive extracellular matrix production by smooth muscle
cells secondary to the chronic hemodynamic stress of hypertension. Hyaline
arteriolosclerosis is a major morphologic characteristic of benign nephrosclerosis, in
which the arteriolar narrowing causes diffuse impairment of renal blood supply, loss of
nephrons, and symmetric contraction of the kidneys.
Hyperplastic arteriolosclerosis. Related to more acute or severe elevations of blood
pressure, hyperplastic arteriolosclerosis is characteristic of, but not limited to, malignant
hypertension. Hyperplastic arteriolosclerosis has onion-skin, concentric, laminated
thickening of the walls of arterioles with progressive narrowing of the lumina. The
laminations consist of smooth muscle cells and reduplicated basement membrane. In
malignant hypertension, these hyperplastic changes are accompanied by fibrinoid
deposits and acute necrosis of the vessel walls, referred to as necrotizing arteriolitis,
particularly in the kidney.
Hypertensive Heart Disease
The diagnosis of hypertensive heart disease is based on the presence of left
ventricular hypertrophy in an individual with a history of hypertension and in whom
other causes of ventricular hypertrophy have been excluded. The stimulus to ventricular
hypertrophy in patients with hypertension is a sustained pressure load on the left
ventricular myocardium.
The essential feature of hypertensive heart disease is left ventricular hypertrophy.
The weight of the heart usually exceeds 450 g. The hypertrophy typically involves the
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ventricular wall in a symmetric, circumferential pattern termed concentric hypertrophy,
with free wall thickness exceeding 2,0 cm. The size of the chamber is normal in the
early stages of hypertensive heart disease, but in long-standing cases some degree of
dilation is common. As left ventricular failure progresses, right ventricular hypertrophy
and dilation may also develop. Coronary artery disease is present in most cases, with its
associated morphologic effects on the myocardium. Microscopically, the cardiac
myocytes are enlarged and contain large, hyperchromatic nuclei. The nuclear changes
are caused by tetraploidy, presumably reflecting abortive attempts at cell replication.
Superimposed ischemic changes, including interstitial fibrosis and recent or remote
infarcts are common.
ISCHEMIC HEART DISEASE
Ischemic heart disease (IHD) refers to a group of closely related syndromes caused
by an imbalance between the myocardial oxygen demand and the blood supply. The
most common cause of IHD is narrowing of the lumina of the coronary arteries by
atherosclerosis, and hence IHD is often termed coronary heart disease or coronary artery
disease. IHD is the single most common cause of death in economically developed
countries of the world.
Depending on the rate and severity of coronary artery narrowing and myocardial
respons, one of four syndromes may develop:
1)various forms of angina pectoris (chest pain),
2)acute myocardial infarction (MI),
3)sudden cardiac death,
4)chronic ischemic heart disease with congestive heart failure.
The term acute coronary syndromes is applied to the spectrum of three acute
catastrophic manifestations of IHD – unstable angina, acute MI and sudden cardiac
death.
Angina pectoris
Angina pectoris– refers to intermittent chest pain caused by reversible ischemia.
Three major variant of angina pectoris are recognized:
1)Typical or stable angina pectoris – refers to episodic chest pain associated with
exertion or some other forms of stress.
2)Prinzmetal angina – refers to angina, that occurs at rest or in some cases, awakens the
patient from sleep.
3)Unstable angina pectoris is characterized by the increased frequence of anginal pain.
It is potentially irreversible myocardial ischemia and hence is sometimes referred to
as preinfarction angina. In most patient it is induced by acute plaque changewith
superimposed partial thrombosis, distal embolization and vasospasm.
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Myocardial infarction
The term MI indicates the development of an area of myocardial necrosis caused by
local ischemia. The location of an MI is determined by the site of the vascular occlusion
and by the anatomy of coronary circulation. Occlusion of the left anterior descending
coronary artery typically caused an infarct in the anterior and apical areas of the left
ventricle and adjacent interventricular septum. Occlusion of the right coronary artery is
responsible for most infarcts involving the posterior and basal portion of the left
ventricle. Occlusion of the left circumflex coronary artery caused an infarct in the lateral
wall of left ventricle.
The size of the infarct is influenced by diameter of artery: occlusion of more proximal
segment of coronary artery produces larger infarcts, occlusion more distal arterial
branches cause smaller infarcts. The extent of the infarct is also influenced by the
degree of collateral circulation that exist at the time of the occlusion.
Myocardial infarcts may involve most of the thickness of the ventricular wall, in
which case they are referred to as transmural infarcts, while those restricted to the inner
one third of the myocardium are designated subendocardial infarcts.
Morphology. For the first 12 hours, no changes are evident on gross examination.
During first 30 minutes there are reversible changes, such as: mitochondrial swelling,
relaxation of myofibrils, loss of enzyme activity and glycogen loss which are
determined by electron microscope and special methods. During 1-2 hours – irreversible
changes: sarcolemmal disruption and electron-dense deposits (EM), few “wavy” fibers
at margun of infarcts (LM). During 4-12 hours: edema and minimal hemorrhages
(microscopically). During 12-24 hours begin gross appearance: slight pallor and
mottling. Microscopically: loss of striations, nuclear pycnosis, “contraction band”
necrosis, neutrophilic infiltration.
1-3 days: grossly-central pallor with hyperemic border,
histologically-complete coagulation necrosis of myofibers, heavy neutrophilic
infiltrate, nuclear lysis.
4-7 days: grossly-pale-yellow center surrounded with hyperemic border,
histologically-macrophages appear, early disintegration and phagocytosis of
necrotic fibers; granulation tissue visible at edge of infarct.
7-14 days: grossly- maximally yellow, soft, shrunken center with red-purple border,
histologically-well-developed phagocytosis, well-established granulation
tissue with new blood vessels and collagen deposition.
2-8 weeks: grossly-grey-white, firm scar.
histologically-increased collagen deposition.
Complications:
1)Arrhytmias – abnormalities in cardiac rhythm.
2)Left ventricular failure – with hypotension, which may progress to pulmonary edema
with respiratory failure.
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3)Cardiogenic shock – severe pump failure.
4)Myocardial rupture: a)transmural infarct may lead to rupture of ventricular wall with
hemopericardium or cardiac tamponade (usually fatal),
b)papillary muscle rupture,
c)rupture of ventricular septum.
5)Mural thrombosis with systemic thromboembolism.
6)Ventricular aneurism – may be complicated with mural thrombosis.
7)Pericarditis (fibrinous or hemorrhagic).
8)Progressive infarction – extension of initial infracted area to adjacent muscle.
Sudden Cardiac Death
Sudden cardiac death has been defined in many different ways, ranging from
instantaneous death to death occurring within 24 hours of the onset of symptoms.
Sudden death can be caused by a wide range of diseases, including heart diseases,
pulmonary embolism, ruptured aortic aneurism, disorders of the central nervous
system and infections. The most common cause of sudden cardiac death is ischemic
heart disease.
The most common cardiac lesions in sudden cardiac death are those of coronary
atherosclerosis and its complications. In most cases the degree of atherosclerosis is
marked, with more than 75% reduction in the cross sectional area of two or more
vessels. A number of studies suggest that acute plaque rupture, followed by coronary
thrombosis and possibly vasospasm, triggers fatal ventricular arrhythmias. However,
occlusive thrombi are absent in over 80% of cases of sudden cardiac death.
Morphologic manifestations of ischemic heart disease, such as recent or remote
myocardial infarctions, patchy myocardial fibrosis, wavy fibers change or contraction
band necrosis, are usually present. Other structural cardiac abnormalities have also been
associated with sudden cardiac death, are: conduction system, abnormalities and
developmental abnormalities of the coronary arteries.
Chronic Ischemic Heart Disease
This term is used to describe the development of progressive congestive heart
failure as a consequence of long-term ischemic myocardial injury.
The coronary arteries invariably contain areas of moderate to severe atherosclerosis.
The heart is enlarged, sometimes to a striking degree, secondary to dilation of all
cardiac chambers. Multiple areas of myocardial fibrosis often including foci of
transmural scarring, are usually present. A moderate degree of hypertrophy of the
remaining myocardium is common. The endocardium is thick and opaque, and thrombi
in varying stages or organization may be adherent to the endocardial surface.
Microscopy revels extensive myocardial fibrosis. Among the remaining myocytes, both
atrophic and hypertrophic fibers are present.
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There are 3 types of chronic ischemic heart disease:
1)atherosclerotic cardiosclerosis (microfocal cardiosclerosis) – associated with
formation of small scars (3-5 mm) – as a result of chronic ischemia in cases of coronary
atherosclerosis;
2)postinfarction cardiosclerosis (macrofocal cardiosclerosis) – associated with
formation of big scars – as a result of acute myocardial infarction;
3)chronic cardiac aneurism – due to massive transmural scarring as a result of acute
myocardial infarction.
CARDIOMYOPATHIES
The term cardiomyopathy could be applied to almost any heart disease, but
convention it is used to describe heart disease resulting from a primary abnormality in
the myocardium.
There are three major clinicopathologic groups: dilated, hypertrophic and
restrictive cardiomyopathy.
Dilated cardiomyopathy.
This diagnisis is applied to a form of cartdiopmyopathy characterized by progressive
cardiac hypertrophy, dilation aand contractile (systolic) dysfunction. The heart is
enlarged and flabby, with weights often exceeding 900 g. The enlargement is caused by
a combination of dilation and hypertrophy of all chambers. The substantial dilation and
poor contractile function cause stasis of blood in the cardiac chambers and predispose to
the development of fragile mural thrombi and subsequent emboli. The microscopic
features are nonspecific and include myocyte hypertrophy, interstitial fibrosis, wavy
fiber change and in some cases a scanty mononuclear inflammatory infiltrate.
Hypertrophic cardiomyopathy.
It is an assymmetric septal hypertrophy and idiopathic hypertrophic subaortic
stenosis, is a cardiac disorder characterized by myocardial hypertrophy, abnormal
diastolic filling and in many cases intermittent ventricular outflow obstruction. The
essential feature of hypertrophic cardiomyopathy is myocardial hyhertrophy, which is
most pronounced in the left ventricle and interventricular septum. In most cases the
interventricular septum is substantially thicker than the free wall of the left ventricle.
Asymmetric septal hypertrophy is often associated with a significant degree of
ventricular outflow obstruction during systole, a feature emphasized in the older
designation idiopathic hypertrophic subaortic stenosis. Microscopically, it is
characterized by a haphazard arrangement of hypertrophied, abnormally branching
myocytes surrounded by increased connective tissue.
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Restrictive cardiomyopathy.
It is a disorder characterized by a primary decrease in ventricular compliance,
resulting in impaired ventricular filling during diastole. The atria are typically dilated.
The ventricles may be of normal size, although some degree of dilation may occur,
particularly in the later stages of the disease. The endocardium is thickened and opaque,
especially in the left ventricle.
The cardiac valves are thickened in some cases, and mural and valvular thrombi may
be present. Histologic sections reveal dense endocardial fibrosis, which extends into the
underlying myocardium.
CONGESTIVE HEART FAILURE
Congestive heart failure is a multisystem derangement that occurs when the heart
is no longer able to eject the blood delivered to it by venous system. Inadequate cardiac
output, also termed forward failure, is almost always accompanied by increased
congestion of the venous circulation (backward failure), because the failing ventricle is
unable to eject the normal volume of venous blood delivered to it during diastole. This
results in an increase in the volume of blood in the ventricle at the end of diastole, an
elevation in end-diastolic pressure within the heart, and, finally, elevated venous
pressure.
Congestive heart pressure may involve the left or right side of the heart or all of the
cardiac chambers. The most common causes of left-sided cardiac failure are systemic
hypertension, mitral or aortic valvular disease, ischemic heart disease, and primary
diseases of the myocardium. The most cause of right-sided heart failure is left
ventricular failure, with its associated pulmonary congestion and elevation in pulmonary
arterial pressure. Right-sided failure may also occur in patients with pulmonic or
tricuspid valve disease.
Systemic morphology of the congestive heart failure:
1)Skin – cyanosis, edema.
2)Subcutaneous fat – anasarca (diffuse edema), cyanosis.
3)Serosal cavities – hydropericardium, hydrothorax, ascites.
4)Lung – brown induration (hemosiderosis and fibrosis)
5)Liver – nutmeg liver leading to cardiac cirrhosis.
6)Kidneys – cyanotic induration.
7)Spleen – cyanotic induration.
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