Atherosclerosis. Definition

1.

ATHEROSCLEROSIS
The lecture was made by Doctor of Medical Sciences
professor Igor Ivanovich Malishev
Translation from Russian into English:
Ryabtseva Anastasia Leonidovna
Translator of the Faculty of Medicine,
MarSU

2. DEFINITION

Atherosclerosis is a chronic slowly progressive
disease which is manifested by focal thickening
of the intima of elastic and muscular-elastic
type arteries due to the deposition of lipids
(lipoproteins) and reactive proliferation of
connective tissue.

3. ETIOLOGY

Nowadays it is generally accepted that
atherosclerosis is a polyetiological disease
associated with the influence of various
exogenous and endogenous factors, among
which hereditary, environmental and
nutritional factors are of primary importance.

4. RISK FACTORS

Age
Hormonal diseases (Diabetes Mellitus)
Physical inactivity, obesity
Smoking
Hypertension

5. PATHOGENESIS

Theories of atherosclerosis
The incrustation theory. According to this theory, atherosclerotic
plaque appears as a result of the organization of blood clots
formed in the vessels.
Myasnikov’s theory. According to this theory, nervous factor
(stressful and conflict situations) plays a big role in the
development of atherosclerosis.
Monoclonal theory. Its authors believe that atherogenesis is based
on the proliferation of smooth muscle cells.
Immunological theory.
Viral theory.
Infiltration theory of Anitchkov N.N. points to the importance of
hypercholesterolemia and hyperlipidemia as a key point in this
disease. The violation of the ratio between LDL and VLDL and
HDL in favor of the first is of greatest importance.

6. PATHOGENESIS

1. In most cases, the development of atherosclerosis is preceded
by atherogenic dyslipoproteinemia.
2. The central link in atherogenesis is damage to the endothelium
(by modified lipoproteins, viruses, immune complexes, bacterial
toxins, etc.) and an increase in vascular permeability.
3. Lipids are captured by endothelial cells (using special
lipoprotein receptors) and transferred to the intima.
4. In the intima, lipoproteins undergo further modification. They
are captured by macrophages, which, when the utilization systems
are depleted, are loaded with lipids and turn into xanthoma cells
5. SMC (smooth muscle cells) migrate to the intima from muscle
layer, synthesize collagen fibers and create the basis of fibrous
plaque.

7. MORPHOGENESIS OF ATHEROSCLEROSIS

The main morphological manifestation of atherosclerosis is a
plaque. In the center of the plaque there is a lipid - protein
detritus. Around the plaque, there is a proliferation of connective
tissue. The atherosclerotic process undergoes stages that have
macroscopic and microscopic features.
Macroscopic atherosclerotic changes:
1. Fatty spots and stripes are small (usually up to 1 cm in
longitudinal size) areas of yellow or yellow-gray color that do not
rise above the surface of the intima.
2. Fibrous (atheromatous) plaques are white or whitish-yellow
solid formations up to 1.5 cm in size, protruding above the surface
of the intima.
3. Complicated lesions (formation of atheromatous ulcers,
deposition of calcium salts (atherocalcinosis)).
Various types of atherosclerotic lesions are usually combined in
one vessel, so you can simultaneously see fatty stripes, fibrous
plaques, atheromatous ulcers and atherocalcinosis.

8. MORPHOGENESIS OF ATHEROSCLEROSIS

Microscopic changes.
Pre-lipid stage is characterized by metabolic changes, increased
permeability and damage to the inner lining of the vessel.
Glycosaminoglycans accumulate in the intima and mucoid
swelling occurs. Lipid drops appear in endothelial cells.
The stage of lipoidosis is characterized by focal deposition of
lipids and proteins in the intima (especially in its superficial
parts). It leads to the formation of fatty spots and stripes. Lipids
accumulate in macrophages and smooth muscle cells that have
specific receptors and are converted into xanthoma (foam) cells.
Liposclerosis is characterized by reactive proliferation of the
connective tissue of the inner lining of the vessel, which leads to
the formation of fibrous plaque.
As a result of the destruction of the plaque cap, an atheromatous
ulcer occurs.
Atherocalcinosis is the final stage of atherosclerosis
morphogenesis.

9. CLINICAL AND ANATOMICAL FORMS

Atherosclerosis is a systemic disease, that is, all elastic and
muscular-elastic arteries are involved in the process. However,
depending on the predominance of the lesion of one or another
organ in a particular vascular basin, there are several clinical and
anatomical forms of atherosclerosis. With each of the forms, two
types of changes can be observed. Slow narrowing of the lumen of
the supplying artery by atherosclerotic plaques leads to chronic
insufficiency of blood supply and ischemic changes like dystrophy
and atrophy of the parenchyma, diffuse or small focal sclerosis.
Acute occlusion of the supplying artery (prolonged spasm,
thrombosis) leads to acute insufficiency of blood supply and the
development of infarction. In some cases, deep atheromatous
ulcers can lead to the development of an aneurysm, i.e. to the
bulging of the artery wall in the affected area, followed by its
possible rupture and bleeding.

10. CLINICAL AND ANATOMICAL FORMS

1. Aortic atherosclerosis is the most common form. Changes are
more pronounced in the abdominal aorta. The aorta is
characterized by the formation of aneurysms, which can be
cylindrical, saccular or hernial. An aneurysm can be true if its wall
is at least one intact aortic membrane. It can be false if the wall of
the aneurysm is adjacent organs or thrombotic masses. There is
also a dissecting aneurysm, when blood exfoliates the middle
membrane from the inner or outer layer, which leads to the
formation of a canal covered with endothelium.
2. Atherosclerosis of the coronary arteries underlies ishemic heart
disease.
3. Atherosclerosis of the cerebral arteries underlies
cerebrovascular diseases.

11. CLINICAL AND ANATOMICAL FORMS

4. Atherosclerosis of the renal arteries leads to two types of
changes. With stenosing atherosclerosis, wedge-shaped areas of
atrophy of the parenchyma are formed. It is followed by collapse
and sclerosis of the stroma (the wedge-shaped form is associated
with the main type of vessels that supply the kidney). Organs
infarction occur when thrombosis joins. It is followed by the
formation of retracted scars in this place. There appears a largelumpy atherosclerotic contracted kidney (atherosclerotic
nephrosclerosis).
5. Atherosclerosis of the intestinal arteries, complicated by a
thrombus, leads to the development of intestinal gangrene.
6. Atherosclerosis of the extremities arteries leads to the
development of muscle atrophy and intermittent claudication
syndrome. With complication of thrombosis, gangrene of the
extremities occurs.

12. HYPERTENSION

Hypertension is a chronic disease, the main
manifestation of which is an increase in blood
pressure. This is a condition in which the
systolic pressure exceeds 140 mm Hg or more
and / or the diastolic pressure exceeds 90 mm
Hg. (as a result of at least three measurements
taken at different times in a calm environment;
in this case, the patient should not take any
medications).

13. SYMPTOMATIC HYPERTENSIONS

There are diseases in which arterial hypertension is one
of the symptoms :
1. Renal hypertension (nephrogenic hypertension),
2. Endocrine hypertension
3. Neurogenic hypertension with increased intracranial
pressure (tumors, brain injury, hemorrhage, abscess),
4. Other hypertensions associated with aortic
coarctation and other vascular abnormalities.
In all these cases, arterial hypertension is not essential
hypertension.
We can state about hypertension disease when arterial
hypertension is the only manifestation of the disease.

14. VARIANTS OF HYPERTENSION

1. Benign hypertension, which is characterized by a slow course
and moderate increase in blood pressure (the level of diastolic
pressure is not more than 110 - 120 mm Hg). This form is
characterized by arteriolosclerosis and arteriolohyalinosis, leading
to atrophic and sclerotic changes.
2. Malignant hypertension, which is characterized by a significant
increase in blood pressure (the level of diastolic pressure exceeds
110 - 120 mm Hg). This form of the disease progresses rapidly and
within 1 - 2 years leads to death. This form is characterized by
fibrinoid vascular necrosis and organ changes associated with it;
most often the disease ends in the development of renal failure.

15. ETIOLOGY OF HYPERTENSION

A number of factors play a role in the occurrence of
hypertension:
1. Genetic predisposition (pathology, mutation,
malformations of about 20 genes responsible for blood
pressure are proven) .
2. Chronic psycho-emotional overstrain (frequent
stress, conflict situations, negative experiences) and
excessive consumption of table salt are significant in
the development of hypertension. Obesity, smoking,
physical inactivity also play a role.

16. PATHOGENESIS OF HYPERTENSION

The theory of G.F. Lang and A.L. Myasnikov: a decrease in the
inhibitory effect of the cortex on the subcortical centers (a stable
focus of excitation is created in the nervous system in the region of
the vasoconstrictor centers). Causes: chronic psychoemotional
overstrain. Vasoconstriction occurs as a result of this.
Theory of A. Guyton and contributors: the initial factor in the
development of hypertension is considered to be a decrease in the
ability of the kidneys to excrete sodium ions and water. The tone
of the vessels increases, sensitization to the action of pressor
impulses arises. This theory considers increased consumption of
table salt as the main triggering factor of arterial hypertension.
Membrane theory of Y.V. Postnov and S.N. Orlov. The main factor
in the development of hypertension is the hereditary factor. A
generalized defect of the membrane pumps of the cell, as a result
of which there is an increase in the content of calcium and sodium
in the cytoplasm of smooth muscle cells.

17. MALIGNANT FORM OF HYPERTENSION

Malignant form is manifested by hypertensive crises i.e. the
episodes of a sharp increase in blood pressure due to spasm of
arterioles. Men are more affected at the age of 35-50 years.
Typical manifestations of a crisis are thrombosis, plasma
impregnation and fibrinoid necrosis of the arterioles walls in
various organs, which leads to multiple infarctions.
Arteriolonecrosis of the renal vessels is typical for malignant
hypertension. Arterioles and capillary loops of the glomeruli
undergo fibrinoid necrosis. In response, organ sclerosis develops
(Fara's malignant nephrosclerosis). Macroscopically, the surface of
the organ becomes often fine-grained. Fara’s malignant
nephrosclerosis progresses rapidly and leads to renal failure.

18. BENIGN FORM OF HYPERTENSION

There are three stages in the course of this
disease.
The first, preclinical stage is characterized by a
temporary increase in blood pressure.
Morphological changes are minimal: there is
hypertrophy of the muscle layer and elastic
structures of arterioles and their small
branches, morphological features of arterioles
spasm. There is a slight hypertrophy of the left
ventricle.

19. BENIGN FORM OF HYPERTENSION

2nd stage is extensive changes in the arteries. It is characterized by
a persistent increase in blood pressure. The most typical are the
changes in arterioles and muscle-type arteries. Hypoxic damage to
the elements of the vascular wall, an increase in its permeability
with plasma impregnation develop as a result of long-term,
repeated spasm with the outcome of arteriolosclerosis or
arteriolohyalinosis.
Elastofibrosis develops in vessels of the elastic and muscularelastic type. Elastofibrosis is accompanied by splitting of the inner
elastic membrane and subsequent sclerosis.
Atherosclerosis also develops in the arterioles, which is facilitated
by arterial hypertension.
All the described changes in blood vessels lead to a thinning of
their walls and a narrowing of their lumen.

20. BENIGN FORM OF HYPERTENSION

In the second stage, myocardial hypertophy increases,
the heart mass can reach 900 - 1000 grams ("bovine
heart"). The thickness of the left ventricular wall
reaches 2 - 3 cm. The resulting relative insufficient
blood supply of the myocardium, which is aggravated
by organic changes in the vessels, leads to the
development of dystrophic changes in cardiomyocytes
and myogenic expansion of cardiac cavities and the
development of diffuse small focal cardiosclerosis,
which underlies cardiac decompensation.

21. BENIGN FORM OF HYPERTENSION

The third stage is secondary changes in organs due to
changes in arteries and impaired intraorgan blood
circulation. Secondary changes in organs can occur
gradually against the background of arterial occlusion
due to arteriolosclerosis (or arteriolohyalinosis) and
atherosclerosis. This leads to parenchymal atrophy and
organ sclerosis. In case of thrombosis joining, spasm or
fibrinoid necrosis and acute changes like infarction and
hemorrhages occur. In the cerebral vessels, fibrinoid
necrosis of arterioles leads to the development of
microaneurysms, the rupture of which threatens with
intracerebral hemorrhages.

22. Clinical and anatomical forms

The cardiac form of hypertension underlies IHD.
The cerebral form of hypertension underlies CVD.
The renal form of hypertension is characterized by acute and
chronic changes. Acute changes include Fara's malignant
nephrosclerosis (with malignant hypertension) and kidney
infarctions.
Chronic changes include the development of arteriolosclerotic
nephrosclerosis (primary contracted kidney). Changes are caused
by sclerosis and hyalinosis of arterioles. Chronic hypoxia of the
renal tissue leads to the collapse of capillary loops, followed by
glomerulosclerosis, atrophy of the tubules, which expand
cystically. Compensatory hypertrophy of the preserved nephrons
occurs, which gives the surface of the kidney a fine-grained
appearance. At the same time, the kidneys decrease in size, the
cortex becomes thinner. Arteriolosclerotic nephrosclerosis leads to
chronic renal failure.

23. ISCHEMIC HEART DISEASE

Ischemic heart disease is a group of diseases resulting
from myocardial ischemia caused by relative or
absolute insufficiency of the coronary circulation.
Ischemic heart disease is essentially a cardiac form of
atherosclerosis and hypertension, therefore the
etiology and pathogenesis of ischemic heart disease are
common with these diseases.
Epidemiology. The disease is widespread, especially in
industrialized countries, where ischemic heart disease
accounts for the bulk of deaths and disabilities caused
by heart disease.

24. RISK FACTORS FOR IHD

Risk factors of the 1st order, when they are
combined, the probability of developing the
disease reaches 60%. These include
hyperlipidemia (dyslipidemia), arterial
hypertension, smoking, hypodynamia, male
gender of the patient.
Risk factors of the 2nd order include old age,
obesity, stress, metabolic disorders such as
diabetes mellitus, gout, etc., deficiency of
magnesium, selenium, zinc, hypercalcemia, etc.

25. IHD CLASSIFICATION

Acute ischemic heart disease
А. Sudden coronary death
B. Sudden cardiac death
C. Acute ischemic myocardial dystrophy
D. Myocardial infarction
Chronic ischemic heart disease
А. Diffuse small focal and postinfarction
cardiosclerosis
B. Heart aneurysm

26. ACUTE ISCHEMIC MYOCARDIAL DYSTROPHY

Occurs with a short-term spasm of the coronary vessels; the
clinical equivalent of AIMD is angina pectoris.
Autopsy reveals edema, minor hemorrhages and the release of
individual neutrophils into the myocardium. The main changes
are detected with electron microscope (swelling of the
mitochondria of cardyomyocytes, destruction of their cristae, a
decrease in the number of glycogen granules) and histochemically
(disappearance of respiratory enzymes) .When the myocardium is
macroscopically treated with nitro blue tetrazolium or tested with
potassium tellurite, the ischemia area is practically not stained
(due to the breakdown of oxidative enzymes) although the intact
myocardium becomes black or dark gray. Polarizing microscopy
reveals overcontracted cardiomyocytes in the ischemic focus.

27. SUDDEN CORONARY DEATH

This pathological condition includes death that occurred in the
first 6 hours after the onset of acute myocardial ischemia as a
result of ventricular fibrillation. As a rule, men die between the
ages of 40 and 60. A mandatory condition is the absence of any
other diseases causing rapid death. The disease is based on a longterm spasm of atherosclerotic stenotic arteries of the heart or their
(less often) thrombosis.
At autopsy, the patient's heart is flabby, with an enlarged cavity of
the left ventricle and with punctate hemorrhages in the
myocardium. The most typical microscopic feature is the
fragmentation of muscle fibers due to dystrophy of
cardiomyocytes. At the ultrastructural level, there is a damage to
the sarcolemma of cardiomyocytes, destruction of mitochondria,
swelling of the sarcoplasmic reticulum. Destruction of elastic
membranes is found in the coronary arteries of the heart, which
indicates coronary spasm.

28. SUDDEN CARDIAC DEATH

Sudden cardiac death includes sudden
coronary death, as well as sudden death in
some other diseases (myocarditis,
cardiomyopathy, coronary artery
malformations, congenital heart defects, etc).

29. ACUTE MYOCARDIAL INFARCTION

Myocardial infarction is a vascular necrosis of the heart
muscle and the most severe variant of acute ischemic
heart disease. In almost every third case, it ends in
death. Most often, the disease develops in the elderly
people, but currently up to 5% of patients are under 40
years of age.
Myocardial infarction undergoes 3 stages. The first
stage is ischemic and lasts 18 hours. Morphological
changes correspond to the changes that occur in acute
ischemic myocardial dystrophy.

30. ACUTE MYOCARDIAL INFARCTION

The necrotic stage occurs 18 - 24 hours after the onset
of ischemia and is characterized by already visible
necrosis. In this case, there is a focus of irregular
shape, which is yellowish-white in color with flabby
consistency and surrounded by a dark brown corolla
(ischemic infarction with a hemorrhagic conversion) in
the myocardium. Microscopically, three areas are
distinguished in the cardiac area: necrotic area,
demarcation area and area of the intact myocardium.
The area of necrosis is represented by cardiomyocytes
with clear features of karyolysis, plasmorexis and
plasmolysis. This area is surrounded by demarcation
inflammation with a large number of
polymorphonuclear leukocytes, which are the most
pronounced on 2 - 3 days from the onset of the disease.

31. ACUTE MYOCARDIAL INFARCTION

Organization stage. After 3 days, the
disintegration of dead muscle cells by
macrophages begins, and individual fibroblasts
appear. By the 7th day, granulation tissue is
formed along the edges of necrosis. Within a
month, the area of necrosis is replaced by
fibrous connective tissue, as the necrotic
muscle tissue dissolves. A scar is formed on the
28th day of the disease (large-focal,
postinfarction cardiosclerosis occurs).

32. ACUTE MYOCARDIAL INFARCTION

According to localization, there are infarctions of the anterior,
posterior and lateral walls of the left ventricle, interventricular
septum, apex of the heart. There are also extensive infarctions.
In relation to the layer of the heart muscle, there are transmural
(most frequent), subendocardial, intramural, and subepicardial
myocardial infarction.
Depending on the temporal features of the onset of myocardial
infarction, there is a primary (acute) myocardial infarction which
occurs within 4 weeks (28 days) before scar formation, reinfarction which develops 4 weeks after an acute one (i.e. when
postinfarction cardiosclerosis develops at the site of the primary
infarction) and relapsing, occurring within 4 weeks after primary
infarction or re-infarction.

33. ACUTE MYOCARDIAL INFARCTION

Atypical variants of myocardial infarction course are
possible. With irradiation of pain into the abdominal
cavity, a picture of "acute abdomen" appears
(abdominal form of myocardial infarction). The patient
may have false symptoms of acute cerebrovascular
accident (cerebral form). With pain in the stomach, the
abdominal form is described. In a number of cases (in
old people, physically strong people, alcohol abusers,
in patients with diabetes mellitus), a painless form of
myocardial infarction may occur.

34. ACUTE MYOCARDIAL INFARCTION

Complications:
Heart aneurysm formation
Myomalacia with rupture of the heart wall
followed by tamponade of the pericardial
cavity with outflowing blood
Dressler's postinfarction syndrome (dry
pericarditis, pleurisy, pneumonitis).

35. CHRONIC ISCHEMIC HEART DISEASE

This concept includes postinfarction (large focal) cardiosclerosis,
diffuse small focal cardiosclerosis and chronic heart aneurysm.
A scar resulting from the organization of infarction has the
appearance of a whitish focus of solid consistency, irregular
shape, surrounded by a hypertrophic myocardium.
With diffuse small focal cardiosclerosis in the myocardium,
multiple, small (up to 1 - 2 mm in diameter) foci of whitish
connective tissue are observed on the cut
Chronic aneurysm of the heart is formed from unexploded acute
(or as a result of protrusion) of postinfarction scar tissue under
blood pressure. In 75% of cases, the aneurysm is localized in the
anterior - lateral wall of the left ventricle and the apex of the heart.
The heart is enlarged, with a bulging, thinned wall of the left
ventricle in the aneurysm, represented by fibrous tissue.

36. CEREBROVASCULAR DISEASES

Classification.
Diseases of the brain with ischemic injury
1. Ischemic encephalopathy
2. Ischemic cerebral infarction
3 Hemorrhagic cerebral infarction
Intracranial hemorrhage
1. Intracerebral
2. Subarachnoid
3. Mixed
Hypertensive cerebrovascular diseases
1. Lacunar changes
2. Subcortical leukoencephalopathy
3. Hypertensive encephalopathy.

37. CEREBROVASCULAR DISEASES

Ischemic damage
1. Transient disorders are based on stenosing atherosclerosis of
cerebral vessels. As a result, parts of the brain experience chronic
ischemia and cerebral atrophy occurs. It is clinically manifested by
increasing dementia and ends with senile marasmus (atrophic
encephalopathy)
2. Cerebral infarctions. The causes are spasm, thrombosis,
embolism. In most cases, ischemic infarction develops in the brain.
Macroscopically, the area of necrosis begins to be determined only
after 6 - 12 hours. It has an irregular shape and is represented by
structureless and sharply increased moisture of the brain tissue
("focus of softening"). Microscopically, the infarction site is a focus
of colliquative necrosis.
Less often, infarction is impregnated with erythrocytes. In this
case, it is an infarction with hemorrhagic impregnation.

38. CEREBROVASCULAR DISEASES

3. Intracerebral hemorrhages are divided into
intracerebral (hypertensive), subarachnoid
(aneurysmal) and mixed (parenchymal and
subarachnoid).
Intracerebral hemorrhages develop when
microaneurysms rupture in places of bifurcation of
intracerebral arteries in patients with essential
hypertension (with the formation of hematoma), and
also as a result of diapedesis (petechial hemorrhages,
hemorrhagic impregnation).
Subarachnoid hemorrhages occur due to rupture of
aneurysms of large cerebral vessels of an
atherosclerotic, inflammatory, congenital and
traumatic nature.

39. CEREBROVASCULAR DISEASES

Hypertensive cerebrovascular diseases develop in people with
hypertension.
Lacunar changes are represented by a lot of small, rusty cysts in
the area of the subcortical nuclei.
Subcortical leukoencephalopathy is accompanied by subcortical
axonal loss.
Hypertensive encephalopathy occurs in patients with a malignant
form of hypertension and is accompanied by the development of
fibrinoid necrosis of the vascular walls.
The terms stroke or brainstroke are used in the clinical practice. A
stroke is understood as a number of pathological processes.
- hemorrhagic stroke: hematoma, hemorrhagic impregnation,
subarachnoid hemorrhage;
ischemic stroke: ischemic and hemorrhagic cerebral infarction.