BLOOD VESSELS DISEASES

IntroductionVascular wall cells and their response to injuryVascular diseasesAtherosclerosis. Clinical significance, pathogenesis, morphology.Hypertensive vascular disease. Clinical significance, pathogenesis, morphology.The vacuities

Introduction

Diseases of arteries are responsible for more morbidity and mortality than any other type of human disease. Disorders of veins less commonly cause clinically significant problems. Vascular abnormalities cause clinical disease by two principal mechanisms

Narrowing or completely obstructing the lumens, either progressively (e.g., by atherosclerosis) or precipitously (e.g., by thrombosis or embolism).

Weakening of the walls, leading to dilation or rupture.To understand the diseases that affect blood vessels, we first consider some of the anatomic and functional characteristics of these highly specialized and dynamic tissues.

NORMAL ARTERY ANATOMY AND FUNCTION

Size Anatomy Function DiseaseLarge vessels: aorta and elastic arteries

elastic lamellae pressure reservoir

atherosclerosis

Medium vessels:muscular arteries

smooth muscle and elastic laminae

distribute atherosclerosis

Small vessels:     arteries (less than 1

mm.)   arterioles (less than

100)

smooth musclesmooth muscle

distributecontrol flow,

maintainresistance and

control pressure

HypertensionHypertension

 Diabetes

OBJECTIVES: Briefly define the key words. Distinguish the 3 major types of arteriosclerosis:

o atherosclerosis: o arteriolosclerosis: o Monckeberg's sclerosis (medial calcinosis):

For atherosclerosis, describe the gross and microscopic appearances of the lesions, their distribution within the arterial tree, major known predisposing factors and complications.

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Identify the major risk factors for atherosclerosis. Which are avoidable or treatable? What are the other risk factors? Know all these cold.

o Major Risk Factors o Other Risk Factors o Avoidable or Treatable?

Describe in general terms the major complications of arteritis. Describe the complications of deep leg vein thrombosis. Your patient has recurrent venous thrombosis. List the diseases and

conditions commonly associated with or predisposing to venous thrombosis. Differentiate atherosclerotic, syphilitic and dissecting aneurysms by their

common location(s) in the aorta. List the complications of atherosclerotic aortic aneurysm. In what way can hemorrhagic dissection of the aorta clinically mimic acute

myocardial infarction? How might aortic dissection cause myocardial infarction?

KEY WORDS:Arteriosclerosis, atherosclerosis, atheroma, atherosclerotic plaque, fissured

or "cracked" plaque, fatty streak, hyperlipidemia, HDL- and LDL-cholesterol, risk factors. Vasculitis, arteritis, polyarteritis nodosa temporal arteritis, Wegener's granulomatosis, Buerger's disease, Rayneaud's phenomenon, phlebothrombosis, thrombophlebitis, migratory thrombophlebitis, varicose veins, varicocele.

LABORATORY OBGECTIVES: What is an atheroma? Where do atheromas most often occur? What changes may be present grossly in a complicated atherosclerotic

plaque? Discuss the differences between an atherosclerotic aneurysm and a

hemorrhagic dissection (dissecting aneurysm) of the aorta. Which is a "true" aneurysm? Which is a "false (or pseudo) aneurysm? Of these three types of aneurysm; (a) syphilitic, (b) atherosclerotic and (c)

dissecting; which occurs most often in the aortic arch and which in the abdominal aorta?

IMPORTANCE Systemic-- disease at multiple sites Affects vital organs Numerous and common - especially atherosclerosis Mortality high - 25 - 40% of U.S. deaths, thousands crippled;

o 5 year survival as bad as many cancers Cost: millions of dollars in lost productivity and medical costs

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VASCULAR RESPONSES TO INJURY, BY SITE AND SIZE OF ARTERY Injury to the endothelium results in thrombi, thickening, and spasm causing pain

of ischemia and loss of function of organ Injury to the media results in aneurysm, rupture with symptoms of pulsatile

mass, hypotension and pain Injury to the adventitia causes weakening, false aneurysm with resulting lump

(hematoma), pain Large vessels are sites for aneurysm and rupture Medium sized arteries thicken and narrow, or thrombose, to cause ischemia Small arteries and arterioles: same (arteriolar narrowing can cause

hypertension) Capillaries: petechial hemorrhage, microthrombi (DIC), narrowing in diabetes

Congenital AnomaliesAberrations of the usual anatomic pattern of branching and anastomosing are important in surgery, during which an unexpected vessel can be injured. They are rarely symptomatic, except in the coronary arterial tree. Among other diverse congenital vascular anomalies, several have importance: developmental or berry aneurysms, and arteriovenous fistulas or aneurysms.

ArteriosclerosisArteriosclerosis (literally, "hardening of the arteries") is a generic term for

thickening and loss of elasticity of arterial walls. Three patterns of arteriosclerosis are recognized; they vary in pathophysiology and clinical and pathological consequences. Atherosclerosis, the most frequent and important pattern, will be discussed first

and in detail below. Mönckeberg medial calcific sclerosis is characterized by calcific deposits in

muscular arteries in persons older than age 50. The radiographically visible, often palpable calcifications, do not encroach on the vessel lumen.

Arteriolosclerosis affects small arteries and arterioles. There are two anatomic variants, hyaline and hyperplastic, both associated with thickening of vessel walls with luminal narrowing that may cause downstream ischemic injury. Most often associated with hypertension and diabetes mellitus, arteriolosclerosis will be described later in this chapter in the section on hypertension.

AtherosclerosisAtherosclerosis is characterized by intimal lesions called atheromas, or

atheromatous or fibrofatty plaques, which protrude into and obstruct vascular lumens and weaken the underlying media. They may lead to serious complications. Global in distribution, atherosclerosis overwhelmingly contributes to more mortality-approximately half of all deaths-and serious morbidity in the Western world than any other disorder. Epidemiologic data on atherosclerosis are usually presented in terms of frequency of the number of deaths caused by ischemic heart disease (IHD).

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NATURAL HISTORY AND MAIN CONSEQUENCESThe American Heart Association classification divides atherosclerotic lesions into six types, beginning with isolated foam cells ("fatty dots"), through stages of fatty streaks, atheromas, and fibroatheromas, to the complicated lesions.

Schematic summary of the natural history, morphologic features, main pathogenetic events, and clinical complications of atherosclerosis in the coronary arteries

Fibrous Plaque Complicated plaques are raised fibrous plaques showing on or more of the following features.

1. Calcification.

The process by which organic tissue becomes hardened by a deposit of calcium salts within its substance.

2. Haemorrhage.

The escape of blood from the vessels.

3. Ulceration.

A local defec of the surface of an organ or tissue, which is produced by the sloughing of inflammatory necrotic tissue.

4. Thrombosis.

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Fatty streaks are the earliest lesion of atherosclerosis. They are composed of lipid-filled foam cells. They are not significantly raised and thus do not cause any disturbance in blood flow. Fatty streaks begin as multiple yellow, flat spots less than 1 mm in diameter that coalesce into elongated streaks, 1 cm long or longer. They contain T lymphocytes and extracellular lipid in smaller amounts than in plaques. Fatty streaks appear in the aortas of some children younger than age 1 year and all children older than age 10 years, regardless of geography, race, sex, or enviroment. Coronary fatty streaks begin to form in adolescence and at anatomic sites that may be prone to develop plaques. The relationship of fatty streaks to atherosclerotic plaques is complex. Fatty streaks are related to the known risk factors of atherosclerosis in adults (especially serum lipoprotein cholesterol concentrations and smoking), and some experimental evidence supports the concept of the evolution of fatty streaks into plaques. Fatty streaks, however, often occur in areas of the vasculature that are not particularly susceptible to developing atheromas later in life. Moreover, they frequently affect individuals in geographic locales and populations in which atherosclerotic plaque is uncommon. Thus, although fatty streaks may be precursors of plaques, not all fatty streaks are destined to become fibrous plaques or more advanced lesions. Atherosclerotic plaques develop primarily in elastic arteries (e.g., aorta, carotid, and iliac arteries) and large and medium-sized muscular arteries (e.g., coronary and popliteal arteries). Symptomatic atherosclerotic disease most often involves the arteries supplying the heart, brain, kidneys, and lower extremities. Myocardial infarction (heart attack), cerebral infarction (stroke), aortic aneurysms, and peripheral vascualr disease (gangrene of the legs) are the major consequences of atherosclerosis. Atherosclerosis also takes a toll through other consequences of acutely or chronically diminished arterial perfusion, such as mesenteric occlusion, sudden cardiac death, chronic ischemic heart disease, and ischemic encephalopathy.In small arteries, atheromas can occlude lumens, compromise blood flow to distal organs, and cause ischemic injury. Plaques can undergo disruption and precipitate thrombi that further obstruct blood flow. In large arteries, plaques encroach on the subjacent media and weaken the affected vessel wall, causing aneurysms that may rupture. Moreover, extensive atheromas can be friable, and shed emboli into the distal circulation.

Morphology. The key processes in atherosclerosis are intimal thickening and lipid accumulation. An atheroma (derived from the Greek word for gruel) or atheromatous plaque consists of a raised focal lesion initiating within the intima, having a soft, yellow, grumous core of lipid (mainly cholesterol and cholesterol esters), covered by a firm, white fibrous cap. Also called fibrous, fibrofatty, lipid, or fibrolipid plaques, atheromatous plaques appear white to whitish yellow and impinge on the lumen of the artery. They vary in size from approximately 0.3 to 1.5 cm in diameter but sometimes coalesce to form larger masses. Atherosclerotic lesions usually involve only a partial circumference of the arterial wall ("eccentric" lesions) and are patchy and variable along the vessel

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length. Focal and sparsely distributed at first, atherosclerosis lesions become increasingly numerous and diffuse as the disease progresses.

In the characteristic distribution of atherosclerotic plaques in humans the abdominal aorta is usually much more involved than the thoracic aorta, and lesions tend to be much more prominent around the origins (ostia) of major branches. In descending order (after the lower abdominal aorta), the most heavily involved vessels are the coronary arteries, the popliteal arteries, the internal carotid arteries, and the vessels of the circle of Willis. Vessels of the upper extremities are usually spared, as are the mesenteric and renal arteries, except at their ostia. Neverthe less, in an individual case, the severity of atherosclerosis in one artery does not predict the severity in another. In an individual, and indeed within a particular artery, lesions at various stages often coexist.

Atherosclerotic plaques have three principal components: (1) cells, including SMCs, macrophages, and other leukocytes; (2) ECM, including collagen, elastic fibers, and proteoglycans; and (3) intracellular and extracellular lipid). These components occur in varying proportions and configurations in different lesions. Typically, the superficial fibrous cap is composed of SMCs and relatively dense ECM. Beneath and to the side of the cap (the "shoulder") is a cellular area consisting of macrophages, SMCs, and T lymphocytes. Deep to the fibrous cap is a necrotic core, containing a disorganized mass of lipid (primarily cholesterol and cholesterol esters), cholesterol clefts, debris from dead cells, foam cells, fibrin, variably organized thrombus, and other plasma proteins. Foam cells are large, lipid-laden cells that derive predominantly from blood monocytes (tissue macrophages), but SMCs can also imbibe lipid to become foam cells. Finally, particularly around the periphery of the lesions, there is usually evidence of neovascularization (proliferating small blood vessels). Typical atheromas contain relatively abundant lipid. Nevertheless, many so-called fibrous plaques are composed mostly of SMCs and fibrous tissue.

Consequences of atheroma 1. reduction of blood flow through arteries2. predisposition to thrombosis (if fibrous cap over plaque breaks down,

collagen fibres of abnormal intima are exposed to circulatingblood which initiates formation of thrombus) - this thrombus may occlude a small vessel causing infarction, or break off a large vessel

3. bleeding into a plaque - blood may dissect into centre of plaque causing it to balloon into vessel lumena dnre reduce blood flow (this is occasionally seen in coronary arteries leading to MI)

4. weakening of vessel wall and aneurysm formation (media progressively becomes replaced by non-contractile inelastic collagen which weakens wall and there is generalised dilatation of artery over a period of years to form an aneurysm)

Plaques generally continue to change and progressively enlarge through cell death and degeneration, synthesis and degradation (remodeling) of ECM, and organization of thrombus. Moreover, atheromas often undergo calcification. Patients with advanced coronary calcification appear to be at increased risk for coronary events.

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The advanced lesion of atherosclerosis is at risk for the following pathological changes that have clinical significance:

Focal rupture, ulceration, or erosion of the luminal surface of atheromatous plaques may result in exposure of highly thrombogenic substances that induce thrombus formation or discharge of debris into the bloodstream, producing microemboli composed of lesion contents (cholesterol emboli or atheroemboli).

Hemorrhage into a plaque, especially in the coronary arteries, may be initiated by rupture of either the overlying fibrous cap or the thin-walled capillaries that vascularize the plaque. A contained hematoma may expand the plaque or induce plaque rupture.

Superimposed thrombosis, the most feared complication, usually occurs on disrupted lesions (those with rupture, ulceration, erosion, or hemorrhage) and may partially or completely occlude the lumen. Thrombi may heal and become incorporated into and thereby enlarge the intimal plaque.

Aneurysmal dilation may result from ATH-induced atrophy of the underlying media, with loss of elastic tissue, causing weakness and potential rupture, discussed later.

EPIDEMIOLOGY AND RISK FACTORSVirtually ubiquitous among most developed nations, atherosclerosis is much

less prevalent in Central and South America, Africa, and Asia. The mortality rate for ischemic heart disease (IHD) in the United States is among the highest in the world and is approximately five times higher than that in Japan. Nevertheless, IHD has been increasing in Japan and is now that country's second leading cause of death. Moreover, Japanese who immigrate to the United States and adopt the lifestyles and dietary customs of their new home acquire the predisposition to atherosclerosis typical of the American population.

The prevalence and severity of the disease among individuals and groups-and therefore the age when it is likely to cause tissue or organ injury-are related to a number of factors, some constitutional but others acquired and potentially controllable.

Risk Factors for AtherosclerosisMajor Lesser, Uncertain, or NonquantitatedNonmodifiableIncreasing age ObesityMale gender Physical inactivityFamily history Stress ("type A" personality)Genetic abnormalities Postmenopausal estrogen deficiency  High carbohydrate intakePotentially ControllableHyperlipidemia AlcoholHypertension Lipoprotein Lp(a)Cigarette smoking Hardened (trans)unsaturated fat intakeDiabetes Chlamydia pneumoniae

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PATHOGENESISUnderstandably, the overwhelming importance of atherosclerosis has stimulated

enormous efforts to discover its cause. Historically, two hypotheses for atherogenesis were dominant: One emphasized cellular proliferation in the intima, whereas the other emphasized organization and repetitive growth of thrombi. The contemporary view of the pathogenesis of atherosclerosis incorporates elements of both older theories and accommodates the risk factors previously discussed.19,20

This concept, called the response to injury hypothesis, considers atherosclerosis to be a chronic inflammatory response of the arterial wall initiated by injury to the endothelium. Moreover, lesion progression is sustained by interaction between modified lipoproteins, monocyte-derived macrophages, T lymphocytes, and the normal cellular constituents of the arterial wall. Central to this thesis are the following: Chronic endothelial injury, usually subtle, with resultant endothelial

dysfunction, yielding increased permeability, leukocyte adhesion, and thrombotic potential

Accumulation of lipoproteins, mainly LDL, with its high cholesterol content, in the vessel wall

Modification of lesional lipoproteins by oxidation 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 Adhesion of platelets Release of factors from activated platelets, macrophages, or vascular cells that

cause migration of SMCs from media into the intima Proliferation of smooth muscle cells in the intima, and elaboration of

extracellular matrix, leading to the accumulation of collagen and proteoglycans Enhanced accumulation of lipids both within cells (macrophages and SMCs)

and extracellularly. Several aspects of the atherogenic process will now be considered in detail.

CLINICOPATHOLOGIC EFFECTS OF ATHEROSCLEROTIC CORONARY ARTERY DISEASE

The complications of atherosclerotic coronary artery disease occur through impaired coronary perfusion relative to myocardial demand (myocardial ischemia). The vascular changes that may cause ischemia in the heart and other organs involve a complex dynamic interaction among fixed atherosclerotic narrowing of the epicardial coronary arteries, intraluminal thrombosis overlying a disrupted atherosclerotic plaque, platelet aggregation, and vasospasm. These factors and critical events in the clinical manifestations of coronary arterial atherosclerotic disease and its downstream consequences in the myocardium are summarized in Figure 11-5 and discussed in depth in.

HYPERTENSIVE VASCULAR DISEASESystemic and local blood pressure must be tightly regulated. Low pressure

causes inadequate organ perfusion, leading to dysfunction and ultimately death of

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underperfused tissues. In contrast, higher pressures that drive blood flow in excess of metabolic demand provide no benefit but may induce blood vessel and organ dysfunction and damage. Elevated blood pressure is called hypertension. As discussed above, hypertension is a risk factor for atherosclerosis. In this section, we shall discuss first the mechanisms of normal blood pressure control, next the possible mechanisms of hypertension, and finally the pathologic changes in the small blood vessels associated with the disorder.

HYPERTENSIONHypertension is a common health problem with some-times devastating

consequences, and often remains asymptomatic until late in its course. Hypertension is one of the most important risk factors for both coronary artery disease and cerebrovascular accidents; hypertension can lead to cardiac hypertrophy and, potentially, heart failure, aortic dissection, and renal failure.It is widely acknowledged that hypertension is a complex, multifactorial disease that has both genetic and environmental determinants. Molecular pathways underlying blood pressure variation have been recently elucidated, creating possible targets for therapeutic intervention. Nevertheless, the pathogenic mechanisms of hypertension in the majority of affected individuals remain largely unknown.Etiologic classificationa. Primary hypertension (also known as essential hypertension) has an unknown etiology, although the renal mechanisms that affect blood pressure (see section VCD are believed to play some role. Also, risk factors for atherosclerosis have been implicated in the development of primary hypertension (see section IV В 1).b. Secondary hypertension has a specific underlying cause, which often is a renal disease (e.g., renal vascular or parenchymal disease, renin-secreting tumor) or an endocrine disease (e.g., primary aldosteronism, Cushing's disease, pheochromocytoma).Clinical course of hypertensiona. Benign hypertension refers to a chronic and relatively mild increase in systemic arterial blood pressure (to a diastolic level not higher than 110 to 120 mm Hg), which may or may not have an underlying cause. Although the secondary effects of hypertension may not beclinically evident for a long time, benign hypertension may progress to cause serious end-organ effects.b. Malignant hypertension refers to a profound and acute elevation of blood pressure (to a diastolic level higher than 110 to 120 mm Hg), which can develop de novo or as a complication of benign hypertension. In malignant hypertension, the development of end-organ effects of hypertension is accelerated, occurring in a brief period of time.

Pathogenesis of Hypertension. The multiple mechanisms of hypertension constitute aberrations of the

normal physiologic regulation of blood pressure. Arterial hypertension occurs when the relationship between cardiac output and total peripheral resistance is altered. For many of the secondary forms of hypertension, these factors are

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reasonably well understood. For example, in renovascular hypertension, renal artery stenosis causes decreased glomerular flow and pressure in the afferent arteriole of the glomerulus. This (1) induces renin secretion, initiating angiotensin II-mediated vasoconstriction and increased peripheral resistance, and (2) increases sodium reabsorption and therefore blood volume through the aldosterone mechanism. In pheochromocytoma, a tumor of the adrenal medulla, catecholamines produced by tumor cells cause episodic vasoconstriction and thus induce hypertension.

Regulation of Normal Blood Pressure. Blood pressure is proportional to cardiac output and peripheral vascular resistance. Indeed, the blood pressure level is a complex trait that is determined by the interaction of multiple genetic, environmental, and demographic factors that influence cardiac output and vascular resistance. The major factors that determine blood pressure variation within and between populations include age, gender, body mass index, and diet, principally sodium intake.

Cardiac output is highly dependent on blood volume, itself greatly influenced by the whole body sodium homeostasis. Peripheral vascular resistance is determined mainly at the level of the arterioles and is affected by neural and hormonal factors. Normal vascular tone reflects the balance between humoral vasoconstricting influences (including angiotensin II, catecholamines, and endothelin) and vasodilators (including kinins, prostaglandins, and NO). Resistance vessels also exhibit autoregulation, whereby increased blood flow induces vasoconstriction to protect against tissue hyperperfusion. Other local factors such as pH and hypoxia, and the α- and β-adrenergic systems, which influence heart rate, cardiac contraction, and vascular tone, may be important. The integrated function of these systems ensures adequate perfusion of all tissues, despite regional differences in demand.

To summarize, essential hypertension is a complex, multifactorial disorder. Although single gene disorders can be responsible for hypertension in unusual cases, it is unlikely that a mutation at a single gene locus is a major cause of essential hypertension in the larger population. It is more likely that essential hypertension results from the combined effect of mutations or polymorphisms at several gene loci that influence blood pressure, interacting with a variety of environmental factors. Vascular Pathology in Hypertension. Hypertension not only accelerates atherogenesis but also causes degenerative changes in the walls of large and medium arteries that potentiate both aortic dissection and cerebrovascular hemorrhage. Hypertension is also associated with two forms of small blood vessel disease: hyaline arteriolosclerosis and hyperplastic arteriolosclerosis.Morphology

Hyaline Arteriolosclerosis. This vascular lesion consists of a homogeneous, pink, hyaline thickening of the walls of arterioles with loss of underlying structural detail, and with narrowing of the lumen. Encountered frequently in elderly patients, whether normotensive or hypertensive, hyaline arteriolosclerosis is more

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generalized and more severe in patients with hypertension. It is also common in diabetes as part of the characteristic microangiography.The lesions reflect leakage of plasma components across vascular endothelium and excessive extracellular matrix production by SMCs secondary to the chronic hemodynamic stress of hypertension or a metabolic stress in diabetes that accentuates EC injury. 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 (diastolic pressures usually over 120 mm Hg). Hyperplastic arteriolosclerosis has onionskin, concentric, laminated thickening of the walls of arterioles with progressive narrowing of the lumina. With the electron microscope, the laminations are seen to consist of SMCs and thickened and reduplicated basement membrane. In malignant hypertension, these hyperplastic changes are accompanied by deposits of fibrinoid and acute necrosis of the vessel walls, referred to as necrotizing arteriolitis, particularly in the kidney.

EFFECTSA. Cardiovascular1. Heart: Concentric LV hypertrophy              (dilates if progresses to cardiac failure)2. Small vessels & arterioles: Hyaline sclerosis              (fibrinoid necrosis if malignant)3. Aorta, large and medium arteries: Atherosclerosis4. Aorta: Dissecting hemorrhage (dissecting aneurysm).B. Renal1. Benign nephrosclerosis               (arteriosclerosis and hyalin arteriolosclerosis)2. Malignant nephrosclerosis               (fibrinoid necrosis of arterioles, capillaritis in glomeruli).C. Brain & Eyes1. Cerebral infarcts due to large vessel disease (atherosclerosis).2. Lacunar infarcts (due to occlusion/stenosis of lenticulo-striate art.3. Intracerebral hemorrhage (due to rupture of arteries in basal ganglia, pons, cerebellum)4. Retinal hemorrhages, exudates, copper wiring, A-V nicking, papilledema5. Hypertensive encephalopathy

ANEURYSMS AND DISSECTIONSAn aneurysm is a localized abnormal dilation of a blood vessel or the wall

of the heart . CLASSIFICATION

By location: location gives a clue as to etiology (abdominal, thoracic)

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By etiology: atherosclerotic, syphilitic (luetic), "dissecting" traumatic, mycotic, congenital

By appearance: berry, saccular, fusiform ATHEROSCLEROTIC

Age: >50, males 5:1, relatively common Location: abdominal aorta (97%) usually below renals, may involve iliacs,

but may occur in thoracic aorta; Mechanism: atheromas --> medial destruction, ulcerated plaques Presentation: pulsatile abdominal mass or pain; or rupture causes abdominal

pain, swelling and shock; or incidentally on x-ray (calcified wall) Complications:

o rupture (retroperitoneal hemorrhage), o stenosis of ureter by pressure or fibrosis, o occlusion of aortic branch (renal, mesenteric), o embolism (thrombo- or atheromatous).

Rupture related to size: greater than 7cm. -- 80% rupture and die; less than 5 cm. -- rarely ruptures

Diagnosis: Ultrasound - clinical cut-off is 6cm. Therapy is surgery: open damaged aorta, insert prosthetic graft (ususally just

below renals, into both iliacs) SYPHILITIC

Age: >40, males 2.5:1, relatively rare in U.S. Location: Ascending thoracic aorta and arch Mechanism: Tertiary syphilis involves vasa vasorum causes vasculitis, and

medial damage Presentation varies:

o dyspnea, stridor, dysphagia, cough, pain, o congestive heart failure due to aortic insufficiency (AI) o aneurysm can compress esophagus or recurrent laryngeal nerve o symptoms depend on structures involved

Causes of death: o heart failure due to AI o hemorrhage due to rupture

Therapy: surgery - aortic and/or valve replacement

DISSECTING HEMORRHAGE OF THE AORTA a.k.a. Cystic Medial Degeneraltion - a pseudoandurysm

Age: 40-60, males 6:1 Location: 95% have intimal tear in ascending aorta

o 5% have no intimal tear (probably just small) o if hemorrhage extends to aortic branches, can cause differences in

pressure and pulse in arms or legs Types:

o Type A: Most common - begins ascending aorta, extends distally o Type B: Begins distal to subclavian, extends distally (3x better

prognosis than Type A, because does not involve vessels to head)

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Mechanisms: o trauma (deceleration injuries in motor vehicle accidents); o others associated with aortic medial degeneration (e.g., Marfan's

syndrome) or hypertension; o not ordinarily caused by atherosclerosis; o hemorrhage dissects into outer layers of media o can rupture outward to pleural, pericardial cavities, or into

retroperitoneum or re-enter lumen o creates false lumen (e.g., double-barrelled aorta), visible on x-ray

Presentation: o 85% pain in chest, or radiating to back; o usually normal or elevated blood pressure o if coronary artery involved, may have MI and drop pressure; o sensory or motor changes if compromise spinal cord vasculature

Therapy: anti-hypertensives, surgery (usually a prosthetic graft). SACCULAR (BERRY) ANEURYSM

Etiology: Congenital vs. acquired Location: Branch sites in Circle of Willis Incidence: 1-2% of normal persons Multiple in l/2 of cases Complications: thrombosis, leakage,vasospasm, rupture (major cause of

subarachnoid hemorrhage) ARTERIO-VENOUS FISTULA (A-V aneurysm, A-V malformation)

Noncapillary connection between artery and vein May be numerous vessels or an aneurysm Causes: developmental, trauma, rupture, inflammation Significance: important cause of intracranial hemorrhage; some cause heart

failure (due to A-V shunting) MYCOTIC ANEURYSM

Definition: "Mycotic" refers to any infection, not only fungal Mechanism: infection causes destruction of media Complication: Infarcts distally, septic or bland Cause: Sequela of infective endocarditis or endarteritis

When an aneurysm is bounded by arterial wall components or the attenuated wall of the heart, it is called a true aneurysm. Atherosclerotic, syphilitic, and congenital vascular aneurysms and the left ventricular aneurysm that can follow a myocardial infarction are of this type. In contrast, a false aneurysm (also called pseudoaneurysm) is a breach in the vascular wall leading to an extravascular hematoma that freely communicates with the intravascular space ("pulsating hematoma"). The most common false aneurysm is a post-myocardial infarction rupture that has been contained by a pericardial adhesion, or a leak at the junction (anastomosis) of a vascular graft with a natural artery. An arterial dissection arises when blood enters the wall of the artery, as a hematoma dissecting between its layers. Dissections may, but do not always, arise in aneurysmal arteries.

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Aneurysms and dissections are most important when they involve the aorta. Both true and false aneurysms, as well as dissections, can rupture.

The two most important causes of aortic aneurysms are atherosclerosis and cystic medial degeneration of the arterial media. However, any vessel may be affected by a wide variety of disorders that weaken the wall, including trauma (traumatic aneurysms or arteriovenous aneurysms), congenital defects such as those potentiating berry aneurysms, which are small, spherical dilatations, most frequently in the brain; infections (mycotic aneurysms, see below); syphilis; or trauma. Arterial aneurysms can also be caused by systemic diseases, as in some vasculitides (see later).Infection of a major artery that weakens its wall gives rise to mycotic aneurysm. Thrombosis and rupture are possible complications. Mycotic aneurysms may originate either (1) from embolization and arrest of a septic embolus at some point within a vessel, usually as a complication of infective endocarditis; (2) as an extension of an adjacent suppurative process; or (3) by circulating organisms directly infecting the arterial wall.For descriptive purposes, aneurysms can be classified by macroscopic shape and size. Saccular aneurysms are essentially spherical (involving only a portion of the vessel wall) and vary in size from 5 to 20 cm in diameter, often partially or completely filled by thrombus. Alternatively, aneurysms may be fusiform (involving a long segment). Fusiform aneurysms vary in diameter (up to 20 cm) and in length; many involve the entire ascending and transverse portions of the aortic arch, whereas others may involve large segments of the abdominal aorta or even the iliacs. However, these shapes are not specific for any disease or clinical manifestations.Clinical Course. The clinical consequences of AAAs include:

Rupture into the peritoneal cavity or retroperitoneal tissues with massive, potentially fatal, hemorrhage

Obstruction of a vessel, particularly of the iliac, renal, mesenteric, or vertebral branches that supply the spinal cord leading to ischemic tissue injury

Embolism from atheroma or mural thrombus Impingement on an adjacent structure, such as compression of a ureter or

erosion of vertebrae Presentation as an abdominal mass (often palpably pulsating) that simulates a

tumor. The risk of rupture is directly related to the size of the aneurysm.45 Risk varies from zero for a small AAA (less than approximately 4 cm in diameter), to 1% per year for aneurysms measuring 4.0 to 4.9 cm indiameter, 11% per year for aneurysms between 5.0 and 5.9 cm in diameter, and 25% per year for those larger than 6.0 cm. Most aneurysms expand at a rate of 0.2 to 0.3 cm/year, but 20% expand more rapidly. The most important clinical factor affecting aneurysm growth is blood pressure, based on La Place's law describing the wall tension as proportional to both diameter and internal pressure in the lumen. Large aneurysms are managed aggressively; operative mortality for unruptured aneurysms is approximately 5%, whereas emergency surgery after rupture carries a mortality rate of more than 50%. As a reflection of the systemic nature of ATH and its

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complications, patients with AAAs are also at significantly increased risk for myocardial infarction and stroke.The treatment of abdominal and thoracic aortic aneurysms is evolving toward endoluminal approaches using stent grafts (expandable wire frames covered by a cloth sleeve) rather than surgery for some patients

Inflammatory Diseases of Vessels I. INFLAMMATORY DISEASES OF ARTERIES - General Principles

Diseases of arteries vary in manifestations many possible arterial sites of localization;

Arteritis o May present with involvement of any organ systemo Commonly involves multiple organso Due to infection (bacterial, fungal, other) or immune

Inflammation of an arterial vessel may: o Weaken vessel walls, causing aneurysm or rupture o Narrow the lumen, causing ischemia o Damage the endothelium, resulting in thrombosis o Be complicated by arteriosclerosis (e.g., syphilitic aortitis with

secondary atherosclerosis) II. INFLAMMATORY DISEASES OF ARTERIES - Specific Diseases

Idiopathic Necrotizing Arteritis: o Often has allergic or autoimmune basis o Affects muscular arteries, arterioles, or capillaries o Classical example is polyarteritis nodosa, (PAN)

Typical lesion: necrosis of wall, marked inflammation Complications: microaneurysms, rupture, occlusion, infarction Patterns of distribution vary Immunoglobulin and complement alterations vary Some cases associated with Hepatitis B infection

o Kawasaki's disease (muco-cutaneous lymph node syndrome): arteritis in children with skin and lymph node involvement sometimes coronary arteries

Giant Cell (temporal) Arteritis (Giant cells around elastica) o Temporal artery usually, can involve aorta o Can cause blindness o Treated with steroids

Wegener's granulomatosis--triad of vasculitis involving: o Midline granuloma (face, upper respiratory tract) o Lungs--infarct-like necrosis with granulomatous inflammation o Kidneys--same, with hematuria

Thromboangiitis obliterans (Buerger's disease): o Pain and ischemia, legs and arms o Relatively young men o Leads to gangrene of extremities o Genetic predisposition possible o Almost exclusively in smokers

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o May improve if give up smoking o Lesion:

cellular thrombosis with inflammation involves arteries and veins fibrosis around nerves and lymphatics

o No agent has been demonstrated

INFLAMMATORY AND NON-INFLAMMATORY DISEASES OF VEINS Phlebitis: Acute inflammation of veins, usually with thrombosis

o Caused by bacterial, parasitic, physical, chemical, allergic injury o Examples:

Pylephlebitis (portal vein) from abdominal infection (e.g., appendicitis)

Dural sinuses in infections of ear and face Pulmonary veins in pneumonia Iliofemoral veins in puerperal sepsis Hepato-veno-occlusive disease from "bush-teas", chemotherapy Migratory thrombophlebitis (as in Trousseau's syndrome)

Transient attacks, variable sites With internal cancers (e.g., pancreas)

Idiopathic Thrombophlebitis: same as phlebothrombosis (see below)

Phlebothrombosis: Venous thrombosis without inflammation o Usually in deep veins of legs (DVT) or pelvic veins o Exact incidence uncertain, but high (autopsy patients, as high as 60%) o Pain, tenderness, swelling, or may be asymptomatic o Complication: Pulmonary embolus

up to 50% of patients source usually deep veins in thigh for fatal emboli

o Clots usually form in relation to valve cusps (sites of maximum stasis), propagate upward

Varicose Veins (not primarily inflammatory) o Abnormally dilated, tortuous veins o Produced by prolonged increase in intraluminal pressure o Often in relation to injury or defect of the vein proximally o Sites (different names at different sites):

Legs (estimated 20% of population) Clustering in families suggests a structural abnormality,

such as defective valves Complications: Inflammation, thrombosis, stasis

dermatitis, ulceration of the skin Not pulmonary embolism

Perianal (hemorrhoids) Vulva (this and those above may be related to pregnancy) Testis (varicocele, dilatation of pampiniform plexus)

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Esophageal varices (in cirrhosis of liver): varices in distal esophagus, cardia of stomach, and perianal region

occur in cirrhosis of the liver portal hypertension causes porto-systemic anastomoses

Complication: hemorrhage, when varices torn or eroded.

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