Vascular Pathology Copy PDF

DR : Aisha Elhamedi Normal blood vessels  Large (Elastic) arteries: Including aorta , its branches (common carotid ,iliac artery ) and pulmonary arteries;. The media of elastic arteries has a high elastin content, allowing these vessels to expand during systole and recoil during diastole. Puls...

DR : Aisha Elhamedi Normal blood vessels  Large (Elastic) arteries: Including aorta , its branches (common carotid ,iliac artery ) and pulmonary arteries;. The media of elastic arteries has a high elastin content, allowing these vessels to expand during systole and recoil during diastole. Pulsatile flow.  Medium (Muscular) arteries: Including Coronary , popliteal and renal artery. the media is composed predominantly of circumferentially oriented smooth muscle cells. regulate regional blood flow and blood pressure.  Small arteries /arterioles: Only smooth muscle cells. Arterioles are the principal points of physiologic resistance to blood flow (blood pressure ).  Capillaries: are approximately the diameters of a red cell, they have thin walls and slow low blood flow. Site for Exchange between blood and tissues.   Venules / veins: Veins have larger diameters, larger lumens, and thinner and less rigid walls.  Lymphatics : thin-walled channels lined by specialized endothelium; return interstitial tissue fluid and inflammatory cells to the bloodstream. Potential pathway for disease dissemination. Endothelial cells: Endothelial cells form a specialized lining for blood vessels. Synthesis mediators help regulate vasodilation and vasoconstriction, hemostasis, and inflammation on the vessel surface and within the wall Endothelial cells are multifunctional cells: 1-Permeability barrier. 2-Elaboration of prothrombotic, antithrombotic and Fibrinolytic mediators. 3-ECM production. 4-Modulation of blood flow and vasomotor tone. 5-Regulation of inflammation. 6-Regulation of cell growth.  Berry aneurysms : occur in cerebral vessels. If Ruptured causes intra cerebral hemorrhage ( fatal ).  Arteriovenous fistula : Direct connection of arteries and veins with out capillaries. Developmental defects / it can be post trauma (from penetrating injuries ). may rupture, leading to intracerebral hemorrhage. Large or multiple Arteriovenous fistulas leading to high-output cardiac failure. fibro muscular dysplasia : Focal irregular thickening medium and large arteries. including renal, carotid, splanchnic, and vertebral vessels. The cause is unknown , Young women. resulting in luminal stenosis; in the renal arteries, this can be a cause of Reno vascular hypertension.  Sclerosis = hardening Hardening of the arteries due to thickening and loss of elasticity of arterial wall. have Three pattern : 1- Atherosclerosis : clinically significant Disease of large and medial sized artery. 2- Arteriolosclerosis : clinically significant disease of small arteries and arterioles. There are two anatomic variants :Hyaline and hyperplastic ( proliferative ). Most often associated with hypertension and diabetes mellitus. 3- Mönckeberg medial sclerosis : Not clinically significant. Is characterized by calcification of the walls of muscular arteries. Typically involving the internal elastic membrane. Affect older Persons ( > 50 ).  It is a slowly progressive disease affect large and medium sized arteries.  Causes more morbidity and mortality (roughly half of all deaths).  characterized by intimal lesion called atheroma ,(also called atheromatous or atherosclerotic plaque ,  Atherosclerotic lesions are patchy, usually involving only a portion of any given arterial wall and are rarely circumferential; on cross-section, the lesions therefore appear “eccentric”.  the most extensively involved vessels are the lower abdominal aorta, the coronary arteries, the popliteal arteries, the internal carotid arteries, and the vessels of the circle of Willis.  Large elastic arteries (e.g., aorta, carotid, and iliac arteries) and medium- sized muscular arteries (e.g., coronary ,renal and popliteal arteries) are the major targets of atherosclerosis.  Theories explaining atherosclerosis : 1- Insudation hypothesis : lipid infiltration (Virchow 1886 ). Lipid from plasma infiltrate and accumulate in the vessel wall. 2- Encrustation hypothesis : (Rokitansky 1852 ). Small initial mural thrombi are the initial event in the atherosclerosis. 3- Monoclonal hypothesis : ( Benditt 1973 ). Smooth muscle proliferation starting with 1 or 2 cells. 4- reaction to injury hypothesis : ( Russel , Ross &John Glomset 1976 ). Smooth muscle cell proliferation due to release of platelet and monocyte growth factors. 5- Intimal cell mass hypothesis : smooth muscle cell proliferation  Risk Factor:  Constitutional Risk Factors : 1- Genetics: familial hypercholesterolemia. 2- Age : between ages 40 and 60, but may be younger. 3- Gender : male > female (during reproductive life ? Estrogen ) at old age f >m.  Modifiable Major Risk Factors : 1- Hyperlipidemia : hypercholesterolemia ,is a major risk factor for atherosclerosis; The major component of serum cholesterol associated with increased risk is low-density lipoprotein - LDL (bad cholesterol) , is the complex that delivers cholesterol to peripheral tissues including Atheromas. High LDL increased risk. high-density lipoprotein HDL (good cholesterol) , is the complex that mobilizes cholesterol from the periphery (including Atheromas)and transports it to the liver for excretion in the bile Higher levels of HDL reduced risk (protective ).  2- Hypertension : major risk factor for atherosclerosis; both systolic and diastolic levels are important.  3- Cigarette smoking : is a well-established risk factor in men and likely accounts for the increasing incidence and severity of atherosclerosis in women.  4- Diabetes mellitus : induces hypercholesterolemia , and markedly increases the risk of atherosclerosis.  Additional Risk Factors :  Inflammation. Inflammation is present during all stages of atherogenesis and is intimately linked with atherosclerotic plaque formation and rupture. C –reactive protein , plasma CRP is a strong independent marker of risk for MI stroke and sudden death..  Hyperhomocystinemia Is associated with premature vascular disease , congenital and acquired.  Lipoprotein a ( L p (a ) ) level associated with coronary and cerebrovascular disease risk.  Metabolic syndrome : characterized by insulin resistance ,hypertension , dyslipidemia ( elevated LDL and depressed HDL) are all cardiac risk factors, ,hypercoagulability and proinflammatory state may contribute to endothelial dysfunction and/or thrombosis..  Factors affecting hemostasis. :elevated plasminogen activator inhibitor 1 ,Platelet-derived factors as well as thrombin.  obesity and stress( type A personality ).  Pathogenesis of Atherosclerosis : 1- Endothelial injury and dysfunction, causing increased vascular permeability, leukocyte adhesion and thrombosis. 2- Accumulation of lipoproteins (mainly LDL and its oxidized forms) in the vessel wall. 3- Monocyte adhesion to the endothelium at the site of the injury , followed by migration into the intima and transformation into macrophages and foam cells. 4- Platelet adhesion Factor release from activated platelets, macrophages, and vascular wall cells, inducing smooth muscle cell recruitment, either from the media or from circulating precursors , 5- Smooth muscle cell proliferation, extracellular matrix production, and recruitment of T cells (inflammatory cells ). 6- Lipid accumulation both extracellular and within cells (macrophages and smooth muscle cell).  Injury to the endothelium triggers monocyte adhesion, a loosening of endothelial cell junctions, and migration of monocytes beneath the endothelium where they differentiate into macrophages. The more permeable endothelium also permits LDL to enter the intima of the artery, and macrophages begin engulfing the LDL by phagocytosis. After macrophages become laden with lipid from ingesting LDL, they are referred to as "foam cells," and collections of these create fatty streaks  Hyperlipidemia, Hypertension, Smoking, Toxins ,Hemodynamic factors, Immune reactions, Viruses ( herpes and cytomegalo virus ) Endothelial Injury/Dysfunction Monocyte adhesion and emigration into intima Lumen LDL Macrophage Endothelium Cytokines(e.g., LDL IL-1, MCP-1) Intima Oxidized LDL Lipid Foam Cytokines uptake cells T (e.g., interferon- Growth factors cell Internal elastic membrane γ) Media Smooth muscle cells Recruitment and migration of smooth muscle cells  the two most important causes of endothelial dysfunction are hemodynamic disturbances and hypercholesterolemia.  Hemodynamic Disturbances. plaques tend to occur at ostia of exiting vessels, branch points, and along the posterior wall of the abdominal aorta, where there are disturbed flow patterns. Non turbulent Laminar flow stimulates the expression of endothelial gene which inhibit the atherogenesis ( Atheroprotective gene ).  Lipids. Lipids are transported in the bloodstream bound to specific apoproteins (forming lipoprotein complexes). Dyslipoproteinemias are lipoprotein abnormalities include (1) increased LDL cholesterol levels, (2) decreased HDL cholesterol levels, and (3) increased levels of the abnormal lipoprotein.  diabetes mellitus, hypothyroidism, nephrotic syndrome cause hypercholesterolemia.  Morphology : 3 Forms.  Fatty streaks. : Fatty streaks are composed of lipid-filled foamy macrophages. Beginning as multiple minute flat yellow spots.  Atherosclerotic ( fibro lipoid ) Plaque. : intimal thickening and lipid accumulation, which together form plaques, Atheromatous plaques are white-yellow ;  Complicated ( plaque ) lesion. is red-brown. ulcerated plaques Superimposed by Thrombosis ,hemorrhage ,emboli and aneurysm. 🔸The endothelial cells begin to produce cell surface adhesion molecules such as VCAM-1 , causing monocytes and T- lymphocytes to adhere to the endothelium and then migrate beneath it by squeezing between the endothelial cells. Circulating monocytes and T-lymphocytes are attracted to the sites of injury by chemo attractant cytokines (chemokines). 🔸The endothelial cells also change shape, and the tight junctions between endothelial cells loosen, increasing the permeability to uid, lipids, and leukocytes. Lipoprotein particles, and especially low-density lipoprotein (LDL), enter the arterial wall and undergo oxidation. Oxidation of LDL in the arterial wall occurs as a result of its exposure to nitric oxide , macrophages, and some enzymes such as lipoxygenase. Once they have migrated into the intima, monocytes differentiate into macrophages and begin to take up oxidized LDL. Macrophages retain the lipid they take up, and as they become more lipid-laden, they are referred to as "foam cells ". Eventually , the foam cell will undergo apoptosis and die, but the lipid will accumulate in the intima. Normal Aorta with no Fatty Streaks  Aorta with fatty streaks (arrows), associated largely with the Ostia of branch vessels Photomicrograph of fatty streak , demonstrating intimal, macrophage-derived foam cells (arrows).  Atherosclerotic (fibro lipoid ) plaques have three principal components:  (1) smooth muscle cells, macrophages, and T cells;  (2) extracellular matrix, including collagen, elastic fibers, and proteoglycans;  (3) intracellular and extracellular lipid. fibrous cap composed of smooth muscle cells and relatively dense collagen. Beneath and to the side of the cap (the “shoulder”) is a more cellular area containing macrophages, T cells, and smooth muscle cells. Deep to the fibrous cap is a necrotic core, containing lipid (primarily cholesterol and cholesterol esters), debris from dead cells, foam cells (lipid laden macrophages and smooth muscle cells), fibrin, variably organized thrombus, and other plasma proteins. The periphery of the lesions demonstrate neovascularization (proliferating small blood vessels. Plaques generally continue to change and progressively enlarge through cell death and degeneration, synthesis and degradation (remodeling) of extracellular matrix , and organization of any superimposed thrombus. , Atheromas often undergo calcification. Basic structure of an atherosclerotic plaque. FIBROUS CAP (smooth muscle cell macrophages, cells, lymphocytes, collagen, elastin, proteoglycans ,neovascularization NECROTIC CENTER (cell debris, cholesterol crystals, foam cells, calcium) MEDIA fibrous cap , , collagen has been stained stained for elastin (black), demonstrating that the internal and external elastic layer are attenuated and blue (Masson trichrome stain) the media of the artery is thinned neovascularization  Atherosclerotic plaques are susceptible to the following clinically important pathologic changes ( complicated ( plaque )lesion ) :  Rupture, ulceration, or erosion : the surface of atheromatous plaques exposes highly thrombogenic substances and leads to thrombosis, which may partially or completely occlude the vessel lumen.  Hemorrhage into a plaque: Rupture of the overlying fibrous cap, or of the thin-walled vessels in the areas of neovascularization, can cause intra plaque hemorrhage; contained hematoma.  Atheroembolism : Plaque rupture can discharge atherosclerotic debris into the bloodstream, producing micro emboli , cholesterol emboli.  Aneurysm formation : Atherosclerosis-induced pressure or ischemic atrophy of the underlying media, with loss of elastic tissue, causes weakness and potential rupture. Atherosclerotic plaque rupture. Plaque rupture without superimpose thrombus Acute coronary thrombosis super imposed on an atherosclerotic plaque with focal disruption of the fibrous cap Here is a coronary artery with atherosclerotic plaques. There is recent hemorrhage into the plaque. This is one of the complications of atherosclerosis. Such hemorrhage could acutely narrow the lumen and produce an acute coronary syndrome with ischemia and/or infarction of the myocardium Ulcerated plaque with dark brown hemorrhage chalky white calcifications  atherosclerotic lesions that are typically responsible for the clinic pathologic manifestations.  Atherosclerotic Stenosis : Narrowing arterial lumens obstructing blood flow.  Acute Plaque Change: Rupture/fissuring , Erosion/ulceration, Hemorrhage into the atheroma,.  Thrombosis : partial or total thrombosis occluding blood flow. Mural thrombi in a coronary artery can also embolize.  Aneurysm rupture.  Vasoconstriction :  Clinical effect :  Aorta : aneurysm ,thrombosis and embolization.  Heart : myocardial infarction , ischemic heart disease.  Brain : cerebral infarction , ischemic encephalopathy.  Small intestine : ischemic bowel disease , infarction.  Lower extremities : intermittent claudication , gangrene.  Stable versus un stable plaques Stable plaques can produce symptoms related to chronic ischemia by narrowing vessel lumens , at peripheral vascular disease (intermittent claudication ), at coronary artery disease ( stable angina ) and at cerebral vascular disease( TIA transient ischemic attack). whereas unstable plaques can cause dramatic and potentially fatal ischemic complications related to acute plaque rupture, thrombosis, or embolization. Stable plaques tend to have a dense fibrous cap, minimal lipid accumulation and little inflammation, whereas “vulnerable” unstable plaques have thin caps, large lipid cores, and relatively dense inflammation , (activated inflammatory cells in Atheromas increase the breakdown of extra cellular matrix components  Major (fatal ) Complication of Atherosclerosis : 1- Myocardial infarction (heart attack), 2- cerebral infarction (stroke), 3-aortic aneurysms, may rupture causing sudden death. 4- peripheral vascular disease (gangrene of the legs).  Atherosclerotic Stenosis. In small arteries, atherosclerotic plaques can gradually occlude vessel lumina, compromising blood flow and causing ischemic injury ( intermittent claudication ).   aneurysm is a localized abnormal dilation of a blood vessel or the heart that may be congenital or acquired. that involve the entire thickness of the wall.  Types : 1- true” aneurysm. involves an attenuated but intact arterial wall or thinned ventricular wall of the heart , including Atherosclerotic, syphilitic, and congenital vascular aneurysms, as well as ventricular aneurysms that follow transmural myocardial infarctions. 2- a false aneurysm (pseudo-aneurysm) a defect in the vascular wall leading to an extravascular hematoma that freely communicates with the intravascular space (“pulsating hematoma”).  aneurysms are classified by macroscopic shape and size. 1- Saccular aneurysms : spherical outpouchings involving only a portion of the vessel wall often contain thrombus. 2- Fusiform aneurysms : diffuse, circumferential dilations of a long vascular segment; can involve extensive portions of the aortic arch, abdominal aorta, or even the iliacs A cross section through the heart reveals a ventricular aneurysm with a very thin wall at the arrow. Note how the aneurysm bulges out. The stasis in this aneurysm allows mural thrombus to formed.  Classification by Etiology : 1- Congenital ( Berry's aneurysms ). 2- Traumatic.( Arteriovenous ) 3- Mycotic.( infection ) 4- Atherosclerotic. ( aorta ) 5- Syphilitic. ( thoracic ) 6- Idiopathic. ( thoracic ) 7- inflammatory. ( Vasculitis – poly arteritis nodosa ) Pathogenesis of Aneurysms : Man above 50 years of age. The two most important causes of aortic aneurysms are atherosclerosis and hypertension. Other factors that weaken vessel walls include trauma, Vasculitis , congenital defects (e.g. berry aneurysms ) and infections( Mycotic aneurysms). Connective tissue disease ( Mar fans syndrome ). Atherosclerotic Aneurysm: aneurysms caused by atherosclerosis and typically occur in the abdominal aorta. hypertension is the most common cause of ascending aortic aneurysms.  Pathogenesis of Aneurysms :  The balance of collagen degradation and synthesis is altered by inflammation and associated proteases. increased matrix metalloprotease- MMP) expression by macrophages degrade all components of the extracellular matrix in the arterial wall.  Weakness of vascular wall through loss of smooth muscle cells : due to  Ischemia of the inner media ( in atherosclerosis -by atheromatous plaque )  outer medial ischemia (in Systemic hypertension - by significant narrowing of the vasa vasorum ).  inadequate (abnormal )connective tissue synthesis ( Marfan syndrome ). Marfan syndrome : is autosomal dominant inheritance disease with mutation in fibrillin -1 gene – (defective synthesis of the scaffolding protein fibrillin ) leads to aberrant TGF-β activity and weakening of elastic tissue ( aneurysm ) Cross-section of Cross section of aortic media from a patient with Marfan syndrome showing elastin fragmentation and areas devoid of elastin that resemble cystic spaces filled with proteoglycans from a patient with Marfan syndrome Normal media showing the regular layered pattern of elastic tissue  Loeys-Dietz syndrome is another cause of aneurysms; mutations in TGF-β receptors lead to defective synthesis of elastin and collagens I and III.  Ehlers-Danlos syndrome : Weak vessel walls due to defective type III collagen synthesis.  Abdominal aorta the most common site of aneurysm.  more frequently in men and in smokers, rarely developing before age 50.  Atherosclerosis is a major cause.  MORPHOLOGY :  Usually positioned below the renal arteries and above the bifurcation of the aorta, can be Saccular or Fusiform.  the aneurysm frequently contains a bland, laminated, poorly organized mural thrombus.  Clinical Features:  Most cases of AAA are asymptomatic.  An enlarging pulsating mass in the abdomen , When large.  abdominal pain  Simulating neoplasm.   Complication of AAA include: 1- Rupture into the peritoneal cavity or retroperitoneal tissues with massive, fatal hemorrhage ( common complication of large aneurysm ). 2- Obstruction of a vessel branching off from the aorta, resulting in ischemic injury to the supplied tissue; for example, iliac (leg), renal (kidney), mesenteric (gastrointestinal tract), or vertebral arteries (spinal cord). 3- Embolism from atheroma or mural thrombus. 4- Impingement on an adjacent structure, for example, compression of a ureter or erosion of vertebrae.  AAA variants : 1- Inflammatory AAA ; ( 5% to 10% )in younger patients , back pain and elevated inflammatory markers (CRP). 2-immunoglobulinG4 (IgG4)-related disease , high plasma levels of IgG4 , have aortitis and periaortitis that weaken the wall give rise to aneurysms. 3- Mycotic AAA.   Thoracic aortic aneurysms are most commonly associated with hypertension, other causes such as Marfan syndrome and syphilis.  Main presentation : 1- respiratory difficulties. 2- difficulty in swallowing. 3- persistent cough due to compression of the recurrent laryngeal nerves. 4- Pain caused by erosion of bone (i.e., ribs and vertebral bodies ). 5- cardiac disease as the aortic aneurysm leads to aortic valve dilation with valvular insufficiency or narrowing the coronary Ostia causing myocardial ischemia. 6- rupture.   Berry ( Saccular )aneurysms : aneurysms in the circle of Willis ( Ant - cerebral artery ). congenital cause (absence of smooth muscle and intimal elastic lamina). common in young hypertensive patients. subarachnoid hemorrhage ( complication ).  Syphilitic aneurysm : age 40 -50 years. manifestation of Tertiary syphilis. Obliterative endarteritis of small vessels including vasa vasorum of the thoracic aorta leads to ischemic injury of the aortic media aneurysmal dilation , common site aortic arch , thoracic aorta. complication : 1- Pressure on surrounding tissue. Dysphagia ,pneumonia and vocal cords paralysis and vertebral erosion. 2- Rupture (hemorrhage ) in to cavity or chest wall. 3- Aortic incompetence.   Mycotic aneurysm : bacterial or fungal infection. weakening of the arterial wall. cerebral arteries can originate : from embolization of a septic embolus, usually as a complication of bacterial endocarditis; as an extension of an adjacent suppurative process; or by circulating organisms directly infecting the arterial wall. Capillary micro aneurysm : ( Charcot –bouchard aneurysms). hypertension and diabetic patient. middle cerebral artery. intra cerebral hemorrhage (complication ).   Aortic dissection occurs when blood separates the laminar planes of the media to form a blood-filled channel within the aortic wall.  occurs principally in two groups of patients: 1- men aged 40 to 60 years with hypertension ( mostly ). 2- younger adults with systemic or localized abnormalities of connective tissue affecting the aorta (e.g., Marfan syndrome).  Dissections can be iatrogenic during coronary catheterization procedures or cardiopulmonary bypass.  pregnancy is associated with aortic dissection ( rare ).  Dissection is unusual in the presence of substantial atherosclerosis or other cause of medial scarring such as syphilis.  Pathogenesis:  Hypertension is the major risk factor for aortic dissection. Aorta shows medial hypertrophy of vasa vasorum associated with degenerative changes such as loss of medial smooth muscle cells and disorganized extracellular matrix.  inherited or acquired connective tissue disorders with defective vascular extracellular matrix (e.g., Marfan syndrome , Ehlers- Danlos syndrome ).  Once a tear has occurred, blood flow under systemic pressure dissects through the media, leading to progression of the hematoma.   Morphology :  An aortic dissection usually initiates with an intimal tear.  In the vast majority of spontaneous dissections, the tear occurs in the ascending aorta.  Clinical Features:  aortic dissections are generally classified into two types : 1- The more common (and dangerous) proximal lesions (called type A dissections ), involving either both the ascending and descending aorta or just the ascending aorta only (types I and II of the DeBakey classification ). 2- Distal lesions not involving the ascending part and usually beginning distal to the subclavian artery (called type B dissections or DeBakey type III).  The classic clinical symptoms : chest and back pain.  The most common cause of death is rupture of the dissection into the pericardial, pleural, or peritoneal cavities. Complication :  cardiac tamponade and aortic insufficiency.  Greater arteries obstruction and ischemic myocardial infarction.  involvement of spinal arteries can cause transverse myelitis.   Summary : Aneurysms are congenital or acquired dilations of the heart or blood vessels that involve the entire thickness of the wall. Complications are related to rupture, thrombosis, and embolization. Dissections occur when blood enters the wall of a vessel and separates the various layers. Complications arise due to rupture or obstruction of vessels branching off the aorta. Aneurysms and dissections result from structural weakness of the vessel wall caused by loss of smooth muscle cells or insufficient extracellular matrix, which can result from ischemia, genetic defects, or defective matrix remodeling.  Definition : blood pressure of more than 140/9o mmHg.  Classified etiologically into : 1- Essential (Primary ) hypertension. 2- Secondary hypertension.  Pathological classification :  Benign hypertension.  Malignant hypertension.  Regulation of arterial blood pressure  Blood pressure is a function of cardiac output and peripheral vascular resistance.  Cardiac output is a function of stroke volume and heart rate. both regulated by the α-and β-adrenergic systems,  Peripheral resistance is regulated predominantly at the level of the arterioles by neural and hormonal inputs. Vasoconstrictors (including angiotensin II, catecholamines, and endothelin) and vasodilators (including kinins, prostaglandins, and nitric oxide.  Kidneys influence peripheral resistance and sodium excretion/retention through the renin-angiotensin system.  Heart (Myocardial natriuretic peptides )are released from atrial and ventricular myocardium in response to volume expansion inhibit sodium resorption in the distal renal tubules sodium excretion and diuresis and also induce systemic vasodilation.  Essential (primary ) hypertension :  Systolic 140 mmhg  diastolic 90 mmhg.  90% to 95% of hypertension is idiopathic (unknown ).  Increased risk of atherosclerosis.  Complication : ( with out treatment ) Cardiac failure with left ventricular hypertrophy and dilatation. Dissecting aneurysms Spontaneous intracranial hemorrhage. Coronary artery atherosclerosis -IHD.  Pathogenesis :  Genetic factors.  Reduced renal sodium excretion.  Vasoconstrictive influences.  Environmental factors like stress, obesity, smoking, physical inactivity, and heavy salt consumption. pathogenesis of essential hypertension  Several underlying conditions :  Renal cause ( renal hypertension ) Renal artery stenosis ,Chronic renal disease and Acute glomerulonephritis.  Endocrine cause. Adrenocortical hyper function (Cushing syndrome , conns syndrome and congenital adrenal hyperplasia.  phaeochromocytoma Catecholamine secreting tumors in the adrenal medulla  Cardiovascular cause - Coarctation of aorta , Polyarteritis nodosa.  Drug therapy. ( corticosteroid, contraceptive pill and NSAID).  Neurologic cause.Psychogenic, Acute stress, including surgery. Renal hypertension :  Two mechanism : Renin dependent hypertension.  renal artery stenosis (atheroma ,fibro muscular dysplasia ) renal ischemia stimulate renin release by the kidney (hyperreninism) This increases circulating angiotensin II (AII) vasoconstriction and aldosterone increase blood volume by enhancing renal reabsorption of sodium and water.  Salt and water overload ( Chronic renal disease, diabetic nephropathy ). Damage nephrons in the kidney the kidney cannot excrete normal amounts of sodium sodium and water retention (increased blood volume, and increased cardiac output ). Malignant hypertension. Rapidly rising severe hypertension small percentage - 5% systolic pressure more than 200 mm Hg, diastolic pressure more than 120 mm Hg). Complication : Cardiac failure ,left ventricular hypertrophy and dilation. Blurred vision due to papilledema and retinal hemorrhage. Hematuria and renal failure due to fibrinoid necrosis of glomeruli. Severe headache and cerebral hemorrhage.  Cause Pathophysiology Acute or chronic left ventricular failure Raised left ventricular pressure raised venous pressure. Mitral stenosis Raised left atrial pressure raised pulmonary venous pressure. Chronic bronchitis and emphysema Hypoxia pulmonary vasoconstriction raised pulmonary venous pressure. Emphysema Loss of pulmonary tissue reduced vascular bed. Recurrent pulmonary emboli Reduction in pulmonary vascular bed available for perfusion. Primary pulmonary hypertension Cause of raised pulmonary pressure unknown  Heart  Ischemic heart disease.  Left ventricular hypertrophy cardiac failure ,spontaneous arrhythmias.  Nervous system  Intracranial hemorrhage ( main cause of death).  Kidney  Proteinuria benign hypertension.  Renal failure malignant hypertension.  Eye :  Hypertensive retinopathy ( retinal hemorrhage , papilledema ).  Vessels ( hypertensive vascular disease )  Hypertensive arteriolosclerosis : 3 morphological forms 1- Hyaline arteriolosclerosis (common ). 2- Hyperplastic (proliferative ) arteriolosclerosis. 3- Necrotizing arteriolitis. Pathogenesis : un clear. Hyaline arteriolosclerosis : physiology - age related. Pathology ( benign hypertension and diabetes -diabetic micro angiography ). Nephrosclerosis , due to chronic hypertension, impairment of renal blood supply and glomerular scarring. Microscopic finding : wall is thickened with deposition of an amorphous pink, hyaline material within the arteriolar wall, resulting in its narrowing. These changes reflect both : plasma protein leakage across injured endothelial cells. increased smooth muscle cell matrix synthesis. 2- Hyperplastic (proliferative ) arteriolosclerosis :  Occurs in malignant hypertension. Also pregnancy ,hemolytic uremic syndrome and scleroderma.  Microscopic finding : - Onion –skin lesion : layers characterized by concentric reduplications of the arteriolar basement membrane by interspersed vascular smooth muscle cells. are accompanied by fibrinoid deposits and vessel wall necrosis 3- Necrotizing arteriolitis : Occurs in sever and malignant hypertension. Effect the small arteries and arterioles. Microscopic finding : hyaline sclerosis. fibrinoid necrosis of vessel wall. Infiltration of neutrophils in adventitia. wall is thickened with increased protein onion-skinning) causing luminal deposition (hyalinized obliteration Hyaline arteriolosclerosis. Hyperplastic arteriolosclerosis  Inflammation of vessels wall.  2Mechanisms ( causes of Vasculitis ) :  Immune mediated inflammation. (Immune complex depostion, anti neutrophilic cytoplasmic antibody ( ANCA ), anti endothelial antibody, ( Non infection Vasculitis) auto reactive T cells)  Direct invasion of vascular wall by infection. (Infection Vasculitis)  Vasculitis associated with other disordered (irradiation, mechanical trauma, and toxins).  Un known etiology.  Vasculitis classification :  Large –Medium –Sized vessels :Takayasu.arteritis and Temporal ( giant cell )arteritis. Medium –Small –Sized vessels : poly arteritis nodosa , Kawasaki disease , , Churg –Strauss syndrome and Wegener's granulomatosis.  Small – Sized vessels : Henoch - schonlein purpura, good posture disease (anti –GBM) , Immune complex Vasculitis (SLE, serum sickness) , Cryoglobulinemia , Churg –Strauss syndrome and Microscopic poly angiitis.  Noninfectious Vasculitis:  The major cause of noninfectious Vasculitis is a local or systemic immune response.  caused by:  Immune complex deposition. seen in systemic lupus erythematosus , Drug hypersensitivity Vasculitis (e.g., penicillin) , Vasculitis secondary to infections. Antibodies to microbial constituents can form immune complexes that circulate and deposit in vascular lesions e.g. polyarteritis nodosa.  Anti neutrophil cytoplasmic antibodies (ANCA ). ANCAs are a heterogeneous group of autoantibodies directed against constituents (mainly enzymes) of neutrophil primary granules, monocyte lysosomes, and endothelial cell s.  Anti-proteinase-3 (PR3-ANCA, previously c-ANCA) , associated with polyangiitis.  Anti-myeloperoxidase (MPO-ANCA, previously p-ANCA) , associated with microscopic polyangiitis and Churg-Strauss syndrome.  Anti endothelial cell antibodies.  Auto reactive T cells.  most common form of Vasculitis.  Affect large to medium -sized arteries.  affects arteries in the head—especially the temporal arteries , also the vertebral and ophthalmic arteries.  Lesions also occur in aorta (giant cell).  Are auto -inflammatory and auto-immune disease.  Pathogenesis: The etiology and pathogenesis of GCA are unknown.  T-cell–mediated immune response  Anti-endothelial cell and anti-smooth muscle cell antibodies.  Pathogenesis of giant cell arteritis. (a) Recruitment and stimulation of antigen-specific T cells by dendritic cells. Interferon-γ regulates the differentiation and function of macrophages. Macrophages in the adventitial layer supply interleukin-1 and interleukin-6, and in the media secrete metalloproteinases. (b) Platelet-derived growth factor and vascular endothelial growth factor are responsible for intimal hyperplasia lumen-occlusive arteritis  Clinical Features:  old age ( rare before age 50 ). More common in female.  fever, fatigue, weight loss (general symptom ).  facial pain or headache (superficial temporal).  diplopia to complete vision loss ( Ophthalmic artery).  Diagnosis depends on biopsy and histologic confirmation  Corticosteroids or anti-TNF therapies are effective.  Morphology ( Microscopic finding ) :  Marked intimal thickening.  reduces the luminal diameter.  medial granulomatous inflammation ( classic type ).  Infiltration of T cells, macrophages and multinucleated giant cells which seen in 75%.  elastic lamina fragmentation.  Giant cell (temporal) arteritis. Giant cells at the degenerated focal destruction of internal elastic internal elastic lamina. lamina (arrow) and intimal thickening  pulseless disease.  a granulomatous Vasculitis of medium and larger arteries.  patients younger than 50.  affect the aorta—particularly the aortic arch and great vessels ( Aortic Arch Syndrome ).  pulmonary artery involvement ( 50 %) coronary and renal arteries also affected.  Morphology :  intimal hyperplasia; severe luminal narrowing and obliterated.  mononuclear infiltrates with perivascular cuffing of the vasa vasorum , intense inflammation in the media, granulomatous inflammation with giant cells , fibrosis and patchy medial necrosis.  Takayasu aortitis shares many attributes with giant cell aortitis , including clinical features and histology  as the disease progresses collagenous scarring, with admixed chronic inflammatory infiltrates in all three layers of the vessel wall,  If aortic root involvement causes dilation and aortic valve insufficiency.  Clinical Features:  Nonspecific symptoms :fatigue, weight loss, and fever.  vascular symptoms :  reduced blood pressure and weak pulses in the carotids and the upper extremities;  ocular disturbances, including visual defects, retinal hemorrhages, and total blindness;  neurologic deficits.  Involvement of the more distal aorta may lead to claudication of the legs.  pulmonary artery involvement can cause pulmonary hypertension.  Narrowing of the coronary Ostia may lead to myocardial infarction, and involvement of the renal arteries leads to systemic hypertension.  Out coming is much worse than giant arteritis.  fibrosis of the arterial media associated with mononuclear infiltrates and inflammatory giant cells small arrow. two cross-sections of the right carotid artery , marked intimal thickening and adventitial fibrosis with minimal residual lumen.  a systemic Vasculitis of small- or medium-sized muscular arteries, typically involving renal and visceral vessels.  no association with ANCA.  30% have chronic hepatitis B ,deposits containing HBsAg-HBsAb complexes.  cause remains unknown.  Morphology :  Segmental ,transmural necrotizing inflammation.  Vessels of any organ ( kidneys, heart, liver and gastrointestinal tract )are involved except lung (pulmonary vessels).  acute phase : transmural inflammation , a mixed infiltrate of neutrophils, eosinophil's, and mononuclear cells, accompanied by fibrinoid necrosis.  Luminal thrombosis can occur.  Later, fibrous (occasionally nodular) thickening of the vessel wall that can extend into the adventitia.  All stages of inflammatory activity could be seen in different vessels or co exist in the same vessels.  Complication : aneurysms , rupture. Impaired perfusion with ulcerations, infarcts, ischemic atrophy, or hemorrhages.  Clinical Features:  a disease of young adults.  can also occur in pediatric.  Ischemia and infarction of affected tissues and organs.  A “classic” presentation :  accelerating hypertension ( renal artery )  abdominal pain and bloody stools.  diffuse myalgia's; and peripheral neuritis ( motor nerves ).  Renal involvement - prominent a major cause of mortality.  PAN is typically fatal;  immunosuppression can remissions or cures in 90% of cases. segmental fibrinoid necrosis and thrombotic occlusion of the lumen of this small artery, part of the vessel wall at the upper right (arrow) is uninvolved.  is an acute febrile systemic Vasculitis , usually self-limited disease.  affect infancy and childhood (80% =4 years old or younger).  Mainly involves medium sized artery and even small arteries.  If coronary artery involvement aneurysms , rupture or thrombosis acute myocardial Infarctions.  is the leading cause of acquired heart disease in children.  The pathogenesis of Kawasaki disease is unknown.  infectious agents (mostly viral ).  The vascular damage is primarily mediated by activated T cells and monocytes/macrophages.  Morphology :  Dense transmural inflammatory infiltrate.  The fibrinoid necrosis is usually less prominent than in PAN.  The acute Vasculitis typically subsides spontaneously or in response to treatment.  healed lesions can also exhibit obstructive intimal thickening.  The cardiovascular Pathologic changes are rarely significant.  Clinical Features:  conjunctival and oral erythema and blistering, edema of the hands and feet, erythema of the palms and soles, rash, and cervical lymph node enlargement ( mucocutaneous lymph node syndrome).  20% of untreated patients asymptomatic coronary arteritis.  giant coronary artery aneurysms rupture or thrombosis , myocarditis ,myocardial infarction and sudden death  treatment with intravenous immunoglobulin (gamma globulin )and aspirin. Necrotizing microvasculitis with granulo lymphmonocytic infiltration  a necrotizing Vasculitis that generally affects capillaries, as well as small arterioles and venules.  also called hypersensitivity Vasculitis or leukocytoclastic Vasculitis.  The skin, mucous membranes, lungs, brain, heart, gastrointestinal tract, kidneys, and muscle can all be involved.  necrotizing glomerulonephritis (90% of patients) and pulmonary capillaritis are particularly common.  it can be a feature of a number of immune disorders, such as Henoch-Schönlein purpura, essential mixed Cryoglobulinemia, and Vasculitis associated with connective tissue disorders Clinical Features:  hemoptysis, hematuria and proteinuria, bowel pain or bleeding, muscle pain or weakness, and palpable cutaneous purpura. Pathogenesis :  antibody responses to antigens such as drugs (e.g., penicillin), microorganisms (e.g., streptococci), heterologous proteins, or tumor proteins , lead to immune complex deposition or trigger secondary immune responses (e.g., the development of MPO -ANCA. Morphology : The Vasculitis resembles that seen in polyarteritis nodosa.  a dense transmural inflammation.  The fibrinoid necrosis is less prominent than in PAN.  the acute form characterized by segmental fibrinoid necrosis of the media , focal transmural necrotizing lesions; absent of granulomatous inflammation.  spare medium-sized and larger arteries involved.  infarcts are uncommon.  In post capillary venules , only infiltrating neutrophils, leukocytoclastic Vasculitis.  little or no immunoglobulin are found in most lesions (“pauci-immune injury )  Small vessel Vasculitis Leukocytoclastic Vasculitis (microscopic polyangiitis) with fragmentation of neutrophils in and around blood vessel walls.  small-vessel systemic necrotizing Vasculitis classically associated with asthma, allergic rhinitis, lung infiltrates, peripheral hyper eosinophilia, and extravascular necrotizing granuloma.  occurs almost exclusively in patients with asthma.  The lung is the most commonly involved organ.  Also called allergic granulomatosis and angiitis, rare disease.  Characteristically accompanied by granulomas and eosinophils.  ANCAs (mostly MPO-ANCAs) in ( < 50 %) ( Autoimmune Vasculitis )  Clinical feature :  palpable purpura, GIT bleeding, and renal focal ,segmental glomerulosclerosis), Myocardial involvement cardiomyopathy 60% - deaths.  May be hyper responsiveness to an allergic stimulus; in patients with asthma  Wegener granulomatosis, is a necrotizing Vasculitis characterized by Necrotizing granulomas of the upper or lower respiratory tract.  small to medium-sized vessels (lungs and upper airways).  Focal necrotizing crescentic, glomerulonephritis ( kidney ).  resembles PAN except respiratory involvement.  Pathogenesis : T-cell–mediated hypersensitivity , PR3-ANCAs ( 95% ).  Morphology :  in lung. Necrotizing granulomatous Vasculitis surrounded by a zone of proliferating fibroblasts ,giant cells and leukocytic infiltrate. alveolar hemorrhage. Late undergo progressive fibrosis and organization.  in kidney : early focal and segmental necrotizing glomerulonephritis focal necrosis with isolated capillary loop thrombosis late crescentic glomerulonephritis (diffuse necrosis with crescent formation ). Clinical Features :  Males at 40 years.  Persistent pneumonitis with bilateral and cavitary infiltrates (95%)  chronic sinusitis(90%)  mucosal ulcerations of the nasopharynx (75%)  evidence of renal disease (80%).  less commonly rashes, myalgias, neural inflammation, and fever.  Treatment with steroids, cyclophosphamide, and more recently TNF antagonists.  segmental, thrombosing, acute and chronic inflammation of medium-sized and small arteries (tibial and radial arteries).  almost exclusively in heavy cigarette smokers, usually before age 35.  Morphology :  focal acute and chronic Vasculitis of small- and medium-sized arteries of hands and feet.  The thrombus can contain small microabscesses composed of neutrophils surrounded by granulomatous inflammation , and may eventually organize and recanalize.  clinical features :  (intermittent claudication),  a superficial nodular phlebitis (venous inflammation).  Chronic extremity ulcerations , gangrene.  Peripheral pulse diminished or absent Thromboangiitis obliterans (Buerger disease). The lumen is occluded by a thrombus containing abscesses (arrow), and the vessel wall is infiltrated with leukocytes  exaggerated vasoconstriction of arteries and arterioles in the extremities, particularly the fingers and toes, but also occasionally the nose, earlobes, or lips.  Induces paroxysmal pallor, and even cyanosis in severe cases;  involved digits classically show “red, white, and blue” color.  Primary Raynaud phenomenon: ( Raynaud disease) : caused by exaggerated central and local vasomotor responses to cold or emotion. The course is usually benign, chronicity atrophy of the skin, subcutaneous tissues, and muscles. Ulceration and ischemic gangrene ( rare ).  Secondary Raynaud phenomenon : caused by  SLE, scleroderma, Buerger disease, atherosclerosis and CREST syndrome (systemic sclerosis )..  Myocardial Vessel Vasospasm :  Excessive constriction of coronary arteries or myocardial arterioles.  cause ischemia and myocardial infarction (persistent vasospasm ). Due to hyper-reactivity of medial smooth muscle cells. high levels of vasoactive mediators , endogenous – (epinephrine) or exogenous – (cocaine or phenylephrine).  vasospasm of cardiac arterial or arteriolar beds ( cardiac Raynaud)  Outcome : sudden cardiac death caused by a fatal arrhythmia or an ischemic dilated cardiomyopathy -called Takotsubo cardiomyopathy“ broken heart syndrome. Varicose Veins ( varicosities ):  abnormally dilated, tortuous veins. Due to Due to prolonged, increased intraluminal pressure vessel dilation and incompetence of the venous valves. or weakness of vessel wall.  superficial veins of the upper and lower leg are commonly involved.  Adult female > male.  obesity and pregnancy (risk factor ).  A familial defective venous wall development ( risk factor ) Clinical Features:  Incompetence of the venous valves leads to stasis, congestion, edema, pain, and thrombosis.  Stasis dermatitis.  ulcerations; Varicosities in two other sites :  lower esophagus (Esophageal varices ).  Anal region (Hemorrhoids ).  Complications : Pain, tenderness, heaviness, inability to walk or stand for long hours Dermatitis which could predispose skin loss Venous ulcers. Development of carcinoma or sarcoma in longstanding venous ulcers Severe bleeding from minor trauma. Blood clotting superficial thrombophlebitis or can extend into deep vein DVT. embolism from these superficial veins is very rare.  Thrombophlebitis and Phlebothrombosis are designations for venous thrombosis and inflammation ,  involvement of deep leg veins accounts (>90%).  periprostatic venous plexus /pelvic venous plexus ( other site ).  large veins in the skull and the dural sinuses(infection or inflammation)  Portal vein thrombosis.(peritoneal infections , (platelet hyperactivity - polycythemia vera).  Prolonged immobilization resulting in venous stasis deep venous thrombosis (DVT) in the lower extremities.  Thrombophlebitis and Phlebothrombosis Thrombophlebitis and Phlebothrombosis are designations for venous thrombosis and in ammation. Phlebothrombosis: Is the term applied when thrombosis ocours in the deep veins in the absence of in ammatory reaction in the veins, it is commonly referred to as Deep Veins Thrombosis ( DVT). Prolonged immobilization resulting in venous stasis (surgery)➡ deep venous thrombosis (DVT) in the lower extremities. Thrombophlebitis: Is the term applied when thrombosis occurs in the veins with in ammatory reaction, the thrombosis being secondary to that in ammation, usually occurs secondary to infecion at the surrounding tissue or occasionally due to trauma to the vein.  Risk factor in leg DVT :  bed rest -postoperative patients.  congestive heart failure.  pregnancy, and obesity. Oral contraceptives.  Systemic hypercoagulability, in patient with cancer - a Para neoplastic syndrome related to elaboration of procoagulant factors by tumor cells , venous thrombosis classically appear in one location, disappear, and then occur in another site, so-called migratory thrombophlebitis (Trousseau sign).  genetic hypercoagulability syndromes.  Pulmonary embolism is the most common serious clinical complication of DVT.  Superior Vena Cava Syndromes : caused by neoplasms that compress or invade the superior vena cava : like Bronchogenic carcinoma and Mediastinal lymphoma obstruction. Clinical manifestation :  Marked dilation of the veins of the head, neck, and arms.  cyanosis.  respiratory distress , (Pulmonary vessels compression ).  Inferior vena cava syndrome :  caused by  neoplasms that compress or invade the inferior vena cava hepatocellular carcinoma and renal cell carcinoma.  thrombosis of the hepatic, renal, or lower extremity veins.  Clinical manifestation : marked lower extremity edema and massive proteinuria.  Lymphangitis represents acute inflammation - bacterial infections into lymphatic's; group A β-hemolytic streptococci are the most common agent, in severe cases, can produce cellulitis or focal abscesses.  Lymphangitis : red, painful subcutaneous streaks and painful enlargement of the draining lymph nodes (lymphadenitis).  Primary ( idiopathic ) lymphedema can occur as simple congenital lymphedema or as the familial Milroy disease.  Secondary ( obstructive )lymphedema : Malignant tumors obstructing. Surgical procedures ( radical mastectomy ). Post irradiation fibrosis. parasites e.g. Filariasis Post inflammatory ( lymphangitis ) obstruction and scarring  Classification of Vascular Tumors  Benign Neoplasms and tumour like  Intermediate-Grade Neoplasms lesion :  Hemangioma. Kaposi sarcoma 1-Capillary hemangioma Hemangioendothelioma 2- Cavernous hemangioma  Lymphangioma.  Malignant Neoplasm 1-Simple (capillary) Lymphangioma Angiosarcoma 2-Cavernous Lymphangioma (cystic hygroma) Hemangiopericytoma  Glomus tumor.  Vascular ectasia.  Reactive vascular proliferations Hemangioma :  Are very common tumor composed of blood-filled vessels.  Most common in infant and children.  Most are present from birth and initially increase in size.but eventually regress spontaneously.  Most common in the head and neck.  Can arise internally ( liver ).  Malignant transformation is rare. Histological and clinical variants:  Capillary hemangioma : most common type; these seen in the skin and mucous membranes.as well as in the liver, spleen, and kidneys. Histologically (thin-walled capillaries with scant stroma ).  Cavernous hemangioma : involve deep structures like liver , Brain and also skin. histologically : unencapsulated mass has infiltrative borders, composed of large, cavernous blood-filled vascular spaces separated by connective tissue stroma. are one component of von Hippel-Lindau disease Intravascular thrombosis and dystrophic calcification - common. locally destructive ,do not spontaneously regress, some may require surgery.  Juvenile hemangioma : Strawberry hemangioma of new born skin.  Pyogenic granuloma : Rapidly growing red pedunculated lesion on skin ,gingival or oral mucosa ( ¼ - history of trauma.  capillary Lymphangioma :  slightly elevated or sometimes pedunculated lesions. occur predominantly in the head neck, and axillary subcutaneous tissues. Histologically, Lymphangioma exhibit networks of endothelium-lined spaces , with absence of red cells.  Cavernous Lymphangioma (cystic hygroma) :  are typically found in the neck or axilla of children.  composed of massively dilated lymphatic spaces lined by endothelial cells and separated by intervening connective tissue stroma containing lymphoid aggregates.  Intermediate-Grade (Borderline) Tumors : Kaposi Sarcoma.  caused by human herpes virus 8 (HHV8).  Classic KS : In older men of Mediterranean, not associated with HIV infection. multiple red-purple skin plaques or nodules, usually in the distal lower extremities. localized to the skin and subcutaneous tissue. Endemic African KS : In HIV-sero negative individuals younger < 40 Indolent or aggressive course common in central Africa lymph node and visceral involvement (prepubertal children ). the prognosis is poor - almost 100% mortality within 3 years.  AIDS-associated (epidemic) KS :  the most common HIV-related malignancy  involves lymph nodes and disseminates widely to viscera.  Transplant-associated KS :occurs in solid organ transplant in the setting of T- cell immunosuppression. Morphology : the cutaneous lesions progress through three stages:  Patches : red-purple macules. Histology irregular endothelial cell–lined vascular spaces with interspersed lymphocytes, plasma cells, and macrophages.  Raised plaques : composed of dermal accumulations of dilated, jagged vascular channels and surrounded by plump spindle cells , extravagated erythrocytes, hemosiderin-laden macrophages, and mononuclear inflammatory cells.  Nodular lesions : composed of sheets of plump , proliferating spindle cells, in the dermis or subcutaneous tissues , slit like spaces containing red cells , mitotic figures are common.  Clinical features :  Classic KS - surgical resection . Radiation f0r multiple lesions and chemotherapy for more disseminated disease Including nodal involvement.  Antiretroviral therapy in HIV patients.  Interferon-α and angiogenesis inhibitors are variably effective. red-purple macules and plaques of sheets of plump, proliferating spindle the skin cells  Malignant Tumors :  Angiosarcoma : is a malignant endothelial neoplasm  affects older adults,  most often involves skin, soft tissue, breast, and liver.  Angiosarcoma can arise in the setting of lymphedema ( radical mastectomy).  Angiosarcoma can induced by radiation and rarely iatrogenically.  Angiosarcoma are locally invasive and can metastasize;  5-year survival rates approach 30%.  Microscopically: from plump, atypical endothelial cells forming vascular channels to wildly undifferentiated tumors with a solid spindled appearance.  The endothelial origin of these tumors can be demonstrated by immunohistochemical staining for CD31 or vonWillebrand factor.  Moderately differentiated Angiosarcoma Immunohistochemical staining for with dense clumps of atypical cells lining the endothelial cell marker CD31, distinct vascular lumens demonstrating the endothelial nature of the tumor cells.  All of the following are well established environmental factors that can be related to hypertension except : 1- Increase salt intake 2- Obesity 3- Physical activity 4- Smoking 5- Stress All of the following pathogenic events are associated with the development of atherosclerosis except : 1- Endothelial cell injury. 2- Lipoprotein depletion. 3- Monocyte adhesion to the endothelium 4- Platelet adhesion. 5- Smooth muscle proliferation.  Which of the following considered primary a large vessel Vasculitis ? 1- Churg- Strauss disease. 2- Giant cell arteritis. 3- Kawasaki disease. 4- Polyarteritis nodosa. 5- Wegener granulomatosis. 29 year old women is diagnosed with hepatitis B infection , she is at greatest risk for developing which of the following : 1- Churg – Strauss disease. 2- hypersensitivity Vasculitis. 3- Poly arteritis nodosa. 4- Takayasu arteritis. 5- Wegener granulomatosis.  All of following are histologic components of the typical atherosclerotic plaque except : 1- B lymphocytes 2- Collagen 3- Macrophages 4- Smooth muscle cells 5 -T lymphocytes