The Blood Vessels

Chapter 7 The Blood Vessels



Ivan Damjanov, MD, PhD




1 What are the most important diseases of the blood vessels?



image Arteriosclerosis, which includes changes induced by aging and hypertension

image Atherosclerosis, a multifactorial disease

image Vasculitis, an inflammatory disease that occurs in several clinicopathologic forms

image Varicose veins

image Vascular tumors


2 Do vascular diseases occur at any age?


Yes, but they occur most often in the elderly.



3 What are the consequences of vascular diseases?


The most important consequences include disturbances of blood flow, such as hypoxia and infarction.



ARTERIOSCLEROSIS



4 What is the difference between arteriosclerosis and atherosclerosis?


Arteriosclerosis is a generic term used for hardening of arteries and arterioles. Atherosclerosis is a multifactorial disease of arteries affected by atheromas.


It should be noted that atherosclerosis affects only the aorta and its major branches. Arteriosclerosis may involve any artery in the body and also may affect arterioles.



5 List some causes of arteriosclerosis



image Atherosclerosis is the most common cause of hardening of the aorta and the major arteries providing blood to the heart, brain, and intestines.

image Mönckeberg medial calcific sclerosis is characterized by idiopathic calcification of the media of muscular arteries. It is of limited clinical significance. For example, calcification of mammary arteries may be seen in mammograms and may be confused with calcification related to breast cancer.

image Arteriolosclerosis is a multifactorial disease related to aging. It can be accelerated by hypertension and diabetes.


6 What are the histologic features of arteriolosclerosis?


Arteriolosclerosis occurs in two histologic forms:


image Hyaline arteriolosclerosis: It is characterized by thickening of the arteriolar wall due to the accumulation of homogeneous material that stains pink in hematoxylin and eosin-stained slides. The nature of this hyaline is unknown. Hyaline arteriolosclerosis is typically found in the kidneys of patients who have diabetes mellitus or benign arterial hypertension.

image Hyperplastic arteriolosclerosis: It is characterized by thickening of the arteriolar wall due to the concentric proliferation of smooth muscle cells, giving the arterioles an “onion skin” appearance. These changes represent an adaptive response of arterioles to severe (“malignant”) hypertension. Arteriolar damage caused by sudden onset of malignant hypertension may cause fibrinoid necrosis.


ATHEROSCLEROSIS



7 What is the hallmark lesion of atherosclerosis?


It is called atheroma, a term derived from the Greek word for porridge and a suffix, -oma, used to denote tumors (e.g., melanoma) and other tumefactions (e.g., hematoma).



8 How does a typical atheroma appear?


A typical atheroma appears as an induration of the vessel’s wall. In an aorta opened at autopsy, it looks like a yellow bump or elevation of the intima. On cross-sectioning, it consists of a soft, lipid-rich center covered with a fibrotic capsule. Atheromas are often partially calcified.



Key Points: Arteriosclerosis and Atherosclerosis



1. Arteriosclerosis, a generic term for hardening of the arteries and arterioles, is used for several chronic arterial diseases, the most important of which are atherosclerosis and hypertension.

2. Atherosclerosis is a multifactorial disease characterized by formation of atheromas.

3. Risk factors, classified as those that can and those that cannot be modified, accelerate the formation of atheromas.

4. The reaction to injury hypothesis provides the best explanation for the pathogenesis of atherosclerosis, but other theories may also elucidate some aspects of this disease.


9 What are the earliest recognizable lesions of atherosclerosis?


Experimental data and autopsy studies indicate that atherosclerosis may begin in two ways: as a fat streak or an intimal smooth muscle cell mass.


image Fatty streaks: Fatty streaks develop from lipid that enters the blood vessel wall from the plasma. This insudation leads to the deposition of lipids in the stroma of the blood vessel, where it is oxidized by free oxygen radicals released from macrophages. Oxidized lipids are taken up by macrophages and smooth muscle cells, which transform into fat-laden foam cells. Accumulation of extracellular and intracellular lipids in the intima accounts for the appearance of fatty streaks that are visible to the naked eye as well as histologically in freshly frozen arteries sectioned with a cryostat.

image Intimal smooth muscle cell masses: These masses are formed from medial smooth muscle cells that grow into the intima. This sequence of events can be induced in animals, and if animals are fed a lipid-rich diet, the smooth muscle cells become lipidized, contributing to the formation of fat streaks. Similar intimal smooth muscle cell masses are seen in humans at the site of arterial branching or bifurcation. It is assumed that these intimal cushions develop in response to injury caused by turbulent blood flow as it passes from one vessel into another of smaller caliber.


10 What happens to fully developed atheromas in the human aorta?


Atheromas may remain unchanged for extended periods of time, and there is evidence that in certain circumstances they can even regress. However, in most cases atheromas will evolve further and show a number of secondary complications, including:


image Expansion: Enlarging atheromas become confluent, and ultimately the entire aorta is covered with atherosclerotic lesions.

image Fibrosis and calcification: Scarring transforms “soft” atheromas into “firm” atheromas, which calcify and become extremely hard and brittle.

image Ulceration and thrombosis: Rupture of the fibrous cap will typically release all the semiliquid material from the central portion of the atheroma. Because this material contains thromboplastin, it will trigger blood clotting, and a thrombus will develop at the site of intimal ulceration.

image Aneurysmatic dilatation: Atheromas may weaken the vessel wall by destroying the elastic tissue and the smooth muscles that maintain the integrity of the normal aorta. Under the influence of blood pressure, such weakened vessel walls will bulge outside and form an aneurysm.


11 How do atheromas cause infarcts?



image Thrombotic occlusion of arteries: Thrombi that form over an ulcerated atheroma may occlude the blood vessel and thus interrupt the blood flow through it. This typically occurs in coronary or cerebral arteries.

image Thromboemboli: Thrombi formed over ulcerated aortic atheromas are not large enough to interrupt the blood flow, and such thrombi do not cause infarcts. However, fragments of aortic thrombi may detach and form emboli, which can cause obstruction of smaller peripheral arteries.

image Cholesterol emboli: Cholesterol crystals released into the arterial circulation during rupture of an aortic atheroma may cause a “shower” of small emboli and numerous microscopic infarcts in various tissue distal to the ruptured atheroma.

image Release of thromboplastin: Thromboplastin released from atheromas may precipitate intravascular coagulation and formation of multiple microthrombi. Such a “localized” disseminated coagulation (DIC) may also cause infarcts by occluding arterioles and capillaries.


12 What are the risk factors for atherosclerosis?


Risk factors can be classified as major or minor. Major factors can be further subdivided into those that are fixed (unavoidable) and those that can be modified.


image Major fixed risk factors include age, male gender, family history of atherosclerosis, and genetic defects in the metabolism of lipids.

image Major risk factors that can be modified include hypertension, hyperlipidemia, diabetes, and smoking.

image Minor risk factors (i.e., factors that contribute to atherosclerosis but on their own have not been proved to cause the disease) are a diet rich in saturated fats and carbohydrates, obesity, physical inactivity, type A personality, and stress.

The most important risk factors for atherosclerosis are included in the mnemonic atheroma:


image Arterial hypertension

image Tobacco

image Heredity (familial hypercholesterolemia)

image Endocrine (diabetes, postmenopausal estrogen deficiency, and hypothyroidism)

image Reduced physical activity (sedentary life)

image Obesity

image Male gender

image Age


13 What is the evidence that hypertension is a major risk factor for atherosclerosis?



image Epidemiologic evidence: Hypertension is the most important risk factor for atherosclerosis in people older than 45 years. Such people have a 5 times higher incidence of ischemic heart disease than normotensive age-matched control subjects.

image Therapeutic trials: Treatment of hypertension reduces the risk of atherosclerosis.


14 What is the evidence that hyperlipidemia is a major risk factor for atherosclerosis?



image Epidemiologic evidence: Hyperlipidemia and especially hypercholesterolemia are the most important risk factors in people younger than age 45 years. Hypercholesterolemia is associated with accelerated development of atherosclerotic lesions, which appear earlier in life and are more pronounced than in people who have normal cholesterol blood levels.

image Genetic studies: Genetic disorders involving various aspects of lipid metabolism are associated with severe atherosclerosis. For example, in familial hypercholesterolemia, an autosomal dominant disease, homozygotes are much more affected than heterozygotes. Homozygotes, who have blood cholesterol concentrations in the range of 600 to 1000 mg/dL, show first clinical signs of atherosclerosis by the time of puberty and if untreated will die by the time they reach 20 years. Heterozygotes, who have cholesterol levels ranging from 250 to 500 mg/dL, develop signs of atherosclerosis by age 40 years.

image Pathologic studies: Atheromas contain large amounts of cholesterol, which presumably plays a role in the evolution of arterial lesions.

image Experimental data: Animals given a high-cholesterol diet develop atherosclerosis more often than those fed a normal diet.

image Therapeutic data: The treatment of hypercholesterolemia can slow the development of atherosclerotic lesions.


15 How do various lipoproteins contribute to hypercholesterolemia?


Low-density lipoprotein (LDL) is the main determinant of the total cholesterol concentration.



16 What are lipoproteins, and how are they classified?


Lipoproteins are spherical particles composed of apoproteins, phospholipids, cholesterol and cholesteryl esthers, and triglycerides. The concentration of cholesterol in various lipoproteins varies, but approximately 70% of total blood cholesterol is contained in low-density lipoproteins (LDL).


Major classes of lipoproteins can be distinguished by ultracentrifugation of plasma:


image High-density lipoproteins (HDLs), which contain less than 25% cholesterol, sediment the fastest.

image LDLs, which contain 70% cholesterol, form a band just above the HDLs.

image Very low-density lipoproteins (VLDLs), which contain 60% endogenous triglycerides and 25% cholesterol, form a band above the LDLs.

image Chylomicrons, which contain 90% dietary triglycerides and 10% cholesterol, are the biggest particles that float on the top of the centrifuged plasma.


17 List the key facts about lipoproteins



image Chylomicrons are formed in the small intestine. Their main function is to transport lipids from the gastrointestinal tract. Lipoprotein lipase of endothelial cells acts on chylomicrons, releasing from them some triglycerides, which enter peripheral fat tissue and muscles. Chylomicron remnants containing cholesterol and the remaining triglycerides are taken up by the liver.

image VLDLs secreted by the liver into the circulation carry triglycerides and cholesterol from the liver into the periphery. Lipoprotein lipase acts on VLDLs, releasing triglycerides that enter fat cells and other cells, leaving behind intermediate-density lipoproteins (IDLs), which are short-lived lipoproteins that transform into LDLs.

image LDLs are the main vehicle for the transport of cholesterol from the liver to the peripheral cells. LDL is removed from blood by receptors on the surface of many cells, such as smooth muscle cells, fibroblasts, and adrenal cortical cells. LDL receptors are expressed on the surface of liver cells, which are instrumental in removing LDL from blood and reinserting it into the intermediary metabolism in the liver cell.

image HDLs are synthesized by the liver and the small intestine. They represent the main reservoir of apoproteins. In addition to donating apoproteins for the synthesis of other lipoproteins, HDLs are important carriers of cholesterol, transporting it from the peripheral tissues into the liver for excretion from the body in bile.


18 What is the difference between “good” and “bad” lipoprotein?


In common parlance, HDL is called good lipoprotein, and LDL is called bad lipoprotein. Approximately 70% of total blood cholesterol is contained in LDL. A high concentration of LDL has been associated with an increased risk of atherosclerosis, whereas high levels of HDL reduce this risk. HDLs mobilize the cholesterol from the periphery and are instrumental in its transport to the liver for excretion from the body.



19 How could one raise HDL levels in blood?


Exercise and alcohol in moderate amounts raise HDL, whereas smoking and obesity lower it. Exercise also reduces blood triglycerides, probably by increasing the activity of lipoprotein lipase.



20 How are hyperlipoproteinemias classified?


Hyperlipoproteinemias are classified into five groups on the basis of laboratory findings. Each group includes congenital and acquired hyperlipoproteinemias. The most common among these five groups are type II hyperlipoproteinemia, characterized by an increased concentration of LDL, and type IV hyperlipoproteinemia, characterized by an increased concentration of VLDL and low HDL.


image Type II hyperlipoproteinemia: It is characterized by marked hypercholesterolemia. It includes several genetic diseases, such as familial hypercholesterolemia due to mutation of the gene for the LDL receptor and some diseases that may lead to the elevation of LDL and cholesterol. Secondary causes include cholesterol-rich diet, biliary tract obstruction, nephrotic syndrome, and hypothyroidism. Type II hyperlipoproteinemia is a major risk factor for coronary heart disease.

image Type IV hyperlipoproteinemia: It is the most common form of hyperlipidemia, marked by hypertriglyceridemia and moderate hypercholesterolemia. It includes several genetic disorders of lipid metabolism, but more often it is secondary to another disorder. Secondary causes include alcohol abuse, diabetes, exogenous and endogenous steroids, oral contraceptives, pregnancy, and stress in general. It poses a moderate risk for coronary heart disease.


21 How does hypertension promote atherosclerosis?


Epidemiologic evidence indicates that hypertension promotes development of atherosclerosis, but the exact mechanism of this effect is not understood. In experimental animals, hypertension promotes the formation of smooth muscle cells and the insudation of lipid into the vessel wall. It may also cause endothelial cell injury. Injured endothelial cells may be more permeable to lipids. At the same time, they may also lose their capacity to control the proliferation of smooth muscle cells after vascular wall injury.


It should be noted that hypertension affects smaller blood vessels and arterioles as well. Even pulmonary hypertension is accompanied by the appearance of fatty streaks in lung arteries. In normal circumstances, the pulmonary artery is not affected by atherosclerosis, in part because of low blood pressure inside this blood vessel.



22 Besides lipoproteins, are there any other clinical laboratory findings that could predict development of atherosclerosis and some of its major complications?


Clinical studies have identified a number of laboratory findings that are abnormal in people suffering from coronary heart disease and other complications of advanced atherosclerosis. These tests may be used as predictors of coronary artery disease. The most promising tests under study are those measuring blood levels of:


image C-reactive protein
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Jul 23, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on The Blood Vessels

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