ATHEROSCLEROSIS

ATHEROSCLEROSIS

·        Atherosclerosis is a multifactorial disease that affects the intima of elastic arteries. The disease is characterized by intramural deposits of lipids, proliferation of vascular smooth muscle cells and fibroblasts, and accumulation of macrophages.

·        Basic lesion is the patchy deposition of yellow lipid in plaques deep in the intima with overlying fibrosis up to 1,5 cm in diameter, protruding into the vessels lumen.  It is called atheroma, i.e. it is essentially an intimal disease.

·        The term AS derives from the combination of athero - (‘porrige’), referring to the soft, lipid-rich material in the center of a typical intimal plaque, and sclerosis (scarring),referring to the connective tissue components.

·        The major clinical syndromes are related with ischemia, which is produced by narrowing of the vascular lumen (coronary heart disease, peripheral vascular disease, cerebral infarction), or from weakening of the arterial wall leading to aneurysm.

·        Atherosclerosis begins early in life and develops progressively over years, it is rarely symptomatic in the first three decades, but thereafter the frequency of clinical atherosclerotic events increases logarithmically. Because of its prevalence, as can be considered epidemic in industrialized nations.

·        Every year approximately 1 million persons in the world experience either a myocardial infarct or sudden cardiac death. Nearly all of them are the result of atherosclerotic coronary disease.

·        Background etiological factors influencing the rich of or susceptibility to atheroma are multiply and interrelated. The major background factors may be grouped into two main categories:

I Endogenous (not modifiable)

1. Sex

Atherosclerotic coronary heart disease is predominantly a disease of men. Especially in younger ages; the prevalence in men in the fourth decade is three times that in women. Possible explanations for the sex differences include levels of estrogenic hormones and higher levels of high-density lipoprotein, which is known to be antiatherogenic, in premenopausal women then in men.

2. Genetic factors (Heredity)

Evidenced in cases with clearly defined abnormalities of lipid metabolism. Apparent genetic roles in familial predisposition to AS may be related to genetic effects on other risk factors, especially hyperlipoproteinemia, hypertension and diabetes mellitus.

II Environmental (modifiable)

1. Diet.

Many studies have demonstrated the specific effects of diet on lipid and lipoprotein levels, including the amount of dietary cholesterol ingested, the total number of calories from carbohydrates, protein and fat, and the intake of alcohol and concentrated sweets (anti-oxidants including red wine reduce the risk).

2. Metabolic diseases.

There are diabetes mellitus, myxedema, nephrosis, xanthomatosis, familial hyper cholesteronemia.

·        Hypertension.

·        Cigarette smoking.

The component of cigarette smoking responsible for the acceleration of atherosclerotic events is not known. It may be related to effects of the cigarette smoking on thrombosis or to increased concentration of carboxygemoglobin in the blood of smokers.

3. Lack of physical exercise.

4. Other risk factors.

Other risk factors suggested being associated with AS obesity, physical activity, hyperglycemia, stress, and coffee consumption.

These factors may act as increased blood lipids-cholesterol and lipoproteins. The risk is correlated with elevated low-density lipoprotein (LDL), formed from the catabolism of very-low-density lipoprotein (VLDL) to a cholesterol ester-protein core that carries some 70% of the total serum cholesterol.  Atheroma is specifically associated with high blood low-density lipoprotein levels (as well as total cholesterol levels). Risk is inversely related to the high-density lipoprotein (HDL) levels, perhaps because HDL helps clear cholesterol from vessel lesion.

Pathogenesis of AS has three stages:

1.      Endothelial injury is accompanied by the attachment of monocytes, platelets, and thrombus formation.

2.      Macrophages in the intima phagocytise lipid and transform into foam cells. Macrophages also secrete growth factors that stimulate the proliferation of smooth muscle cells.

3.      Ruptured atheromas release thrombogenic material into the circulation, causing thrombus for intimal ulceration.

Classification AS has the following microscopically stages (phases):

1.       Pre-lipid stage is characterized by mucoid swelling of intima and accumulation of plasma proteins, and glycosaminoglycanes, the destruction of endothelium and elastic and collagen fibers of intima's basal membrane.

2.       Stage of fatty stripes (lipoidois). Fatty stripes appear on intima due to its lipid infiltration, lipoproteins and proteins fixation. Lipids impregnate intima and are accumulated in macrophages. Macrophages that have accumulated lipid in their cytoplasm appear histologically as csantomic or foam cells. Elastic membranes become swollen, their destruction occurs,

3.       Stage of liposclerosis. Macrophages secrete growth factors and cytokines, which recruit additional monocytes, macrophages and other cells. Cytokines and growth factors also stimulate the proliferation of smooth muscle cells and their ingrowth into the intima from the tunica media. Lipid accumulates not only in macrophages but also in smooth muscle cells. From dead and dying cells, cholesterol is released into interstitial spaces. In the areas of lipidosis a young connective tissue grows and forms a fibrous cap. On the luminal side, atheromas typically covered with an intimal fibrous cap, consisting of fibroblasts, surrounded by collagen, which replaces the normal intimal cells. Macroscopically dense, oval, white formations are observed there.

4.       Stage of atheromatosis is characterized by necrosis of the central part of fibrous cap with forming of amorphous substance (atheromatouse detritis). Atheromas consist of amorphous lipid-rich material and are soft. Cholesterol clefts are recognized by their typical needle-shaped appearance.

5.       Stage of ulceration is characterized by the break of the fibrous cap cover and forming of ulcer with small hemorrhage into plaque.

6.       Stage of atherocalcinosis is characterized by deposition of calcium in ulcerative plaque. Dense and fragile cap is formed due to the cap of connective tissue infiltration with calcium. The calcification of vessels leads to hardening of arteries.  Atheromas weaken the arteries and predispose to formation of aneurysm.

Complicated plaques develop from preexisting fibrous plaques as a result of one of a combination of several pathologic changes that include calcification; ulceration, thrombosis and hemorrhage. The complicated lesion is the most common type of atherosclerotic lesion that produces significant circulatory change and clinical disease.

Clinical-morphological appearances

1. Atherosclerosis of aorta - the most common form. Usually it is not complicated by the thrombosis, thromboembolism and embolism to legs. Development of aortal aneurysm is possible.

2. Atherosclerosis of coronary arteries of heart lead to ischemic heart disease (IHD). May be causes acute infarction.

3. Atherosclerosis of arteries of cerebrum. It’s possible the development of thrombosis. The results are ischemic infarctions of brain, less often the haemorrhage in brain occurs. Dystrophy and atrophy of the brain cortex may develop as result of the long-term ischemia. General chronic ischemia of brain leads to senile dementia. Atherosclerosis of carotides leads to acute local ischemia and cerebral softening (infarction).

4. Atherosclerosis of renal arteries leads to atrophy of parenchyma, or infarction. Outcome is atherosclerotic nephro-cirrhosis.

5. Atherosclerosis of arteries of an intestine is complicated by the thrombosis, leading to the gangrene.

6. Atherosclerosis of arteries of extremities, very often this process is located in femoral arteries. The thrombosis with gangrene of leg is possible. Collateral circulation is usually good; atheroma must be very severe before chronic ischemia with intermittent claudication/or gangrene develops.

Aneurysms

These are localized abnormal dilatations of vascular wall. Most common (and significant) are aortic aneurysms. Morbidity and mortality are secondary to

·        Rupture.

·        Impingement on adjacent structures.

·        Occlusion of proximate vessels by either extrinsic pressure or superimposed thrombosis.

·        Embolism from mural thrombosis.

·        Etiologies of aneurysms include atherosclerosis, cystic medial necrosis (the two most common causes), syphilis, trauma, congenital defects, and infections (mycotic aneurysms).

Morphologically, aneurysms are classified as follows:

·        Berry aneurysm. Spherical dilatation due to congenital wall weakness, generally less than 1.5 cm in diameter, typically in the circle of Willis.

·        Saccular aneurysm. Large spherical dilatation up to 20cm in diameter, often at least partially filled with thrombus. The etiology is usually atherosclerosis.

·        Fusiform (cylindroid) aneurysm. Gradual lumen dilatation generating a spindle-shaped lesion up to 20 cm in diameter, and to the full length of the aorta. AS is the most common cause.

·        Dissecting aneurysm. Blood enters the arterial wall through a tear, usually in the aortic arch, and dissects the layers-typically between the middle and outer thirds of the media.