Blood Vessels Congenital Anomalies Arteriosclerosis Aneurysms And Vasculitides PDF

PATHOLOGY OF BLOOD VESSELS Congenital Anomalies Arteriosclerosis Aneurysm and Dissection Vasculitides DR O.O. WILLIAMS  LEARNING OBJECTIVES 1. Describe the normal anatomy of blood vessels. 2. Describe the pathology of congenital anomalies 1 involving blood vessels. 3....

PATHOLOGY OF BLOOD VESSELS Congenital Anomalies Arteriosclerosis Aneurysm and Dissection Vasculitides DR O.O. WILLIAMS  LEARNING OBJECTIVES 1. Describe the normal anatomy of blood vessels. 2. Describe the pathology of congenital anomalies 1 involving blood vessels. 3. Describe the risk factors, anatomic pathology and 2 complications of arteriosclerosis. 4. Explain the pathogenesis of aneurysm and dissection. 5. Describe the typical clinical presentation, gross and 3 microscopic pathology, immunopathology and pathophysiology of the common vasculitides. 4 NORMAL ANATOMY OF BLOOD VESSELS To fully comprehend the pathogenesis of vascular disorders, it is important to first understand normal blood 1 vessels. Blood vessels are fundamentally all flexible tubes compose 2 d of smooth muscle cells (SMCs) and extracellular matrix (ECM) with an inner luminal face covered by a continuous lining of endothelial cells (ECs). However, the relative 3 amounts of SMCs and ECM and the specific properties of the ECs naturally vary throughout the vasculature depending 4 on unique functional needs. NORMAL ANATOMY OF BLOOD VESSELS To properly accommodate pulsatile flow and higher blood pressures, arte rial walls are thicker than veins and typically invested with several reinforcing1 layers of SMCs. As arteries narrow to arterioles, the ideal ratio of wall thickness to lumen diameter progressively increases to allow more precise regulation of 2 pressure. intravascular Veins, on the other hand, are distensible thin-walled vessels with high capacitance. 3 maximal diffusion, capillaries are essentially single-cell To facilitate linings of ECs lying on a basement membrane. 4  NORMAL ANATOMY OF BLOOD VESSELS Vessel walls are meticulously organized into three concentric layers: intima, media, and adventitia. These distinct layers are present in all vessels but are most apparent in larger vessels and particularly arteries. The intima consists of an Endothelial Cell monolayer on a basement membrane with minimal underlying extracellular matrix ECM; it is separated from the media by a dense elastic membrane called the internal elastic lamina. The media is composed predominantly of SMCs and ECM, surrounded by loose connective tissue, nerve fibres and smaller vessels of the adventitia. An external elastic lamina is present in some arteries and defines the transition between media and adventitia. Diffusion of oxygen and nutrients from the lumen is adequate to sustain thin-walled vessels and the innermost SMCs of all vessels. In large and medium-sized vessels, however, small arterioles within the adventitia (called vasa vasorum — literally, ―vessels of the vessels‖) perfuse the outer half to two-thirds of the media. NORMAL ANATOMY OF BLOOD VESSELS NORMAL ANATOMY OF BLOOD VESSELS ELASTIC ARTERIES ("large arteries") include the aorta and at least the begi nnings of its largest branches. These arteries both propel and dampen the pulse wave. These are distinguished by a preponderance of elastic fibres in th eir media. The subendothelium of their intimal layers thickens over the cours e of life through the accumulation of collagen fibers and myointimal cells. The elastic tissue proliferates here. In older adults, the elastic is largely replaced by collagen. This also results in lengthening and thus tortuosity seen in older people. The adventitia and outer media are nourished by vasa vasorum. All arteries depend on the blood within their lumens to nourish their intima and inner media. NORMAL ANATOMY OF BLOOD VESSELS MUSCULAR ARTERIES ("medium-sized arteries", "distributing arteries") exhibit smooth muscle in their walls, and may expand and contract to regulate the calibre of the lumen and thus the flow of blood. The intima is similar to that of the elastic arteries, and it thickens similarly. Smooth muscle may pass into the intima through fenestrae in the internal elastic membrane. These fenestrae may become wide in old age and be mistaken for damage from previous vasculitis. The media is bounded on either side by an inner and outer elastic membrane. NORMAL ANATOMY OF BLOOD VESSELS SMALL ARTERIES are the major site of autonomic regulation of blood flow, and are the worse affected by hypertension. The wall and lumen have the same thickness. Thickening of the intima occurs here as well. Hyaline arteriolar sclerosis worsens with age, especially with diabetes or hypertension. There's no outer elastic membrane, and the layers become progressive ly less distinct as the arteries get smaller. NORMAL ANATOMY OF BLOOD VESSELS ARTERIOLES continue the anatomy of the small arteries. Two definitions that have been offered: (1) Arterioles have five or fewer layers of smooth muscle; (2) Arterioles have total diameter 100 microns or less. VEINS The muscle in the wall of a vein is thinner, and in the larger veins tends to be less organized. Very large veins have some layers of elastic outside their musc ular layer. In disease, veins do not usually show so much intimal proliferation and fibrosis as do arteries. Lymphatics run very close to arteries (even closer than the veins), and tend to be small and to have thinner walls than the vein that runs with that artery. It's not always possible to tell lymphatics from veins; if the vessel contains red cells, it's most likely a vein. NORMAL ANATOMY OF BLOOD VESSELS NORMAL ANATOMY OF BLOOD VESSELS ENDOTHELIUM : It is permeable to water and the small inorganic ions. It transports small amounts of blood protein by pinocytosis. These are recognised as Weibel-Palade bodies on electron microscopy. It can contract, to regulate capillary flow. It produces some of the subendothelial connective tissue. It also makes substances: (1) Prostacyclin (to keep its surface slippery) (2) Von Willebrand's factor (3) Endothelin (a vasoconstrictor peptide) (4) Endothelial-derived relaxation factor (nitric oxide, EDRF). NORMAL ANATOMY OF BLOOD VESSELS VASCULAR SMOOTH MUSCLE also has special functions. They participate in both normal vascular repair and pathologic processes such as atherosclerosis. When stimulated by various factors, smooth muscles do the following: Proliferate Upregulate ECM collagen, elastin, and proteoglycan production Elaborate growth factors and cytokines  CONGENITAL ANOMALIES Although rarely symptomatic, unusual anatomic variants of blood vessels can cause complications during surgery may occur when a vessel in an unexpected location is injured. Cardiac surgeons and interventional cardiologists must also be familiar with coronary artery variants that can occur in up to 1% to 5% of patients. The common vascular congenital anomalies include: 1) Berry aneurysms These are thin-walled arterial outpouchings in cerebral vessels, classically at branch points around the circle of Willis; they occur where the arterial media is congenitally attenuated and can spontaneously rupture causing fatal subarachnoi d haemorrhage. CONGENITAL ANOMALIES The Circle of Willis with berry aneurysms  CONGENITAL ANOMALIES 2. Arteriovenous (AV) fistulas (malformations) These are abnormal connections between arteries and veins without an intervening capillary bed. They occur most commonly as developmental defects but can also result from rupture of arterial aneurysms into adjacent veins, from penetrating injuries that pierce arteries and veins, or from inflammatory necrosis of adjacent vessels. AV fistulas can be created surgically to provide vascular access for haemodialysis. Extensive AV fistulas can cause high-output cardiac failure by shunting large volumes of blood from the arterial to the venous circulation. CONGENITAL ANOMALIES Arteriovenous malformation  CONGENITAL ANOMALIES 3. Fibromuscular dysplasia is a focal irregular thickening of the walls of medium- and large-sized muscular arteries due to a com bination of medial and intimal hyperplasia and fibrosis. It can manifest at any age but occurs most frequently in young women. The focal wall thickening results in luminal stenosis or can be associated with vessel spasm that reduces vascular flow; in the renal arteries, it can lead to renovascular hypertension. Between the focal segments of thickened wall, the artery often exhibits medial attenuation; vascular outpouchings can develop in these portions of the vessel and sometimes rupture. CONGENITAL ANOMALIES Fibromuscular Dysplasia. The lumen is narrowed by focal thickening of the vessel wall( )  ARTERIOSCLEROSIS Arteriosclerosis literally means ―hardening of the arteries‖; it is a generic term reflecting arterial wall thickening and loss of elasticity. Four distinct types are recognized, each with different clinical and pathologic causes and consequences: Arteriolosclerosis affects small arteries and arterioles and may cause downstream ischaemic injury. Associated with hypertension Mönckeberg medial sclerosis is characterized by the presence of calcific deposits in muscular arteries, usually centered on the internal elastic lamina, and typically in individuals older than 50 years of age. The lesions do not encroach on the vessel lumen and usually are not clinically significant. Fibromuscular intimal hyperplasia is a non-atherosclerotic process that occurs in muscular arteries larger than arterioles. This is predominantly an SMC- and ECM-rich lesion driven by inflammation (as in a healed arteritis or transplant-associated arteriopathy, or by mechanical injury (e.g., associated with stents or balloon angioplasty). Atherosclerosis, from Greek root words for ―gruel‖ and ―hardening,‖ is the most frequent and clinically important pattern. It is associated with lipid cholesterol deposition.  ATHEROSCLEROSIS Atherosclerosis is characterized by intimal lesions called atheromas (or atheromatous or atherosclerotic plaques) that impinge on the vascular lumen and can rupture to cause sudden occlusion. It is a pathological process that causes damage to the aorta, cerebral vasculature, coronary arteries and peripheral arteries. Risk factors Modifiable: Hypertension, diabetes, cigarette smoking, hyperlipidaemia(especially hypercholesterolemia), stress and obesity. Nonmodifiable: age, male gender, family history, genetic abnormalities (LDL receptor gene mutations) Additional factors: Inflammation(C-Reactive Protein levels independently predict the risk for myocardial infarction, stroke, peripheral arterial disease, and sudden c ardiac death, even among apparently healthy individuals)  ATHEROSCLEROSIS Additional factors: Hyperhomocysteinaemia, Metabolic syndrome Lipoprotein (a)  ATHEROSCLEROSIS The currently held view of pathogenesis is embodied in the response-to-injury hypothesis. This model views atherosclerosis as a chronic inflammatory response of the arterial wall to endothelial injury. Lesion progression involves interaction of modified lipoproteins, monocyte derived macrophages, T lymphocytes and the cellular constituents of the arterial wall. According to this model, atherosclerosis results from the following pathogenic events: EC injury— and resultant endothelial dysfunction—leading to increased permeability, leukocyte adhesion, and thrombosis Accumulation of lipoproteins (mainly oxidized LDL and cholesterol crystals) in the vessel wall Platelet adhesion Monocyte adhesion to the endothelium, migration into the intima, and differentiation into macrophages and foam cells Lipid accumulation within macrophages, which respond by releasing inflammatory cytokines SMC recruitment due to factors released from activated platelets, macrophages, and vascular wall cells SMC proliferation and ECM production 1. Chronic endothelial injury With resultant endothelial dysfunction, causing increased permeability, leukocyte adhesion and thrombosis. Accumulation of lipoproteins This is mainly Low-density lipoprotein molecules LDL and its oxidized forms in the vessel wall. LDL becoming oxidized by free radicals, particularly oxygen free (ROS). When oxidized LDL comes in contact with an artery wall, a series of reactions occur to repair the damage to the artery wall caused by oxidized LDL. Monocyte adhesion to the endothelium Followed by migration into the intima and transformation into macrophages and foam cells. The body's immune system responds to the damage to the artery wall caused by oxidized LDL by sending specialized white blood cells (macrophages and T lymphocytes) to absorb the oxidized-LDL forming specialized foam cells. Unfortunately, these white blood cells are not able to process the oxidized-LDL, and ultimately grow then rupture, depositing a greater amount of oxidized cholesterol into t he artery wall. This triggers more white blood cells, continuing the cycle. Various chemotactic and growth factors are released from activated platelets, macrophages and vascular wall cells, inducing SMC recruitment, either from the media or from the circulating precursors.  SMC proliferations and ECM production. Eventually, the artery becomes Inflamed with progressive fibrosis. The cholesterol plaque causes the smooth muscle cells to enlarge and form a hard cover over the affected area. This hard cover is what causes a narrowing of the artery, reduces the blood flow and increases blood pressure. Lipid accumulation occurs both extracellularly and within cells (macrophages and SMC‘s). Accumulation of lipid-containing macrophages in the intima gives rise to ―fatty streaks‖, with further evolution, a fibrofatty atheroma consisting of proliferated SMC, foam cells, extracellular lipid, and ECM is formed. The periphery of the lesions shows neovascularization (proliferating small blood vessels). Plaques generally progressively enlarge over time through cell death and degeneration, synthesis and degradation of ECM (remo deling) and thrombus organization. Atheromas also often undergo calcification COMPLICATIONS OF ATHEROSCLEROSIS 1. Occlusion of vessel 2. Disruption of plaque: Haemorrhage within plaque or rupture or ulceration of plaque (with exposure of the thrombogenic components) can result in thrombus formation. Stable plaques have densely collagenized and thickened fibrous caps with minimal inflammation and negligible underlying atheromatous cores, whereas vulnerable plaques have thin fibrous caps, large lipid cores, and increased inflammation. 3. Emboli: Plaque can break free and be carried in the blood stream farther down the vessel. The above listed complications can lead to ischemia and infarcts of organs. Symptoms, signs, and results depend upon organ supplied. COMPLICATIONS OF ATHEROSCLEROSIS COMPLICATIONS OF ATHEROSCLEROSIS 4. Aneurysm: Atherosclerosis begins as an intimal process, but over time the thickened intima puts pressure on and causes atrophy of the media, often resulting in an aneurysm (i.e., dilation or saccular outpouching of the vessel).This can lead to rupture of the vessel and resultant haemorrhage 5. Peripheral vascular disease Clinical presentation: Claudication, which is characterized by ache or cramping in the extremities with exertion that is relieved by standing still. Patients also have cool extremities, diminished distal pulses, and shiny, hairless skin. Patients with severe peripheral vascular disease have pain at rest. Ischemic ulcerations are a common cause of morbidity.  ANEURYSM AND DISSECTION This is a localised abnormal dilatation of a blood vessel or wall of the heart. When an aneurysm is bounded by the arterial wall components or attenuated wall of heart its called a ―true aneurysm‖. Atherosclerotic, syphillitic and congenital vascular aneurysms and left ventricular aneurysm that can follow a myocardial infarction are true aneurysms are true aneurysms. ―False aneurysm‖ (also called pseudoaneurysm) is a breach in the vascular wall leading to extravascular haematoma that freely communicates with intravascular space (pulsating haematoma). The most common false aneurysms are: 1) Post myocardial infarction rupture 2) Leak at junction(anastomosis) of a vascular graft with a natural artery.  ANEURYSM AND DISSECTION Dissection arises when blood enters the wall of artery a haematoma and dissecting through its layers. Dissections may but do not always arise in aneurysmal arteries. Both true and false aneurysms as well as dissections can rupture. Two most important causes of aneurysms 1) Atherosclerosis 2) Cystic medial degeneration of arterial media Others : Traumatic (arteriovenous aneurysms), saccular (berry) aneurysms, Mycotic (infectious) aneurysms, syphillitic aneurysm, some vasculitides.  ANEURYSM AND DISSECTION Aneurysms can be classified by shape and size Saccular aneurysms: spherical, 5-20cm, often partially or completely filled by thrombus. Fusiform aneurysms: involving a long segment, many involve the entire ascending and transverse portion of the aortic arch. These shapes and sizes are not specific for any disease or clinical manifestations ABDOMINAL AORTIC ANEURYSM Arteriosclerosis the most frequent aetiology. Morphology: Usually positioned below the renal arteries and above the bifurcation of the aorta. It may be saccular of fusiform It is a prime site for the formation of atheroemboli. Pathogenesis : AAAs rarely develop before age 50 years and are more common in men. There is genetic susceptibility to AAA beyond the genetic predisposition to atherosclerosis. As in Marfan syndrome: genetic defects in connective tissue component which is responsible for strength of the aorta. Matrix metalloproteinases (M MPs) produced by macrophages degrade extracellular matric proteins. ABDOMINAL AORTIC ANEURYSM This EC matrix includes (collagens, elastins, proteoglycans, laminin and fibronectin). Decreased levels of tissue inhibitor of metalloproteinases (TIMP) have also been reported in aortic aneurysms. Clinical course: Rupture into the peritoneal cavity or retroperitoneal tissues with massive fatal haemorrhage. Obstruction of vessel (iliac, renal or mesenteric) leading to ischaemic tissue injury. Embolism from atheroma or mural thrombus. Impingement on adjacent structures such as compression of the ureter or erosion of the vertebrae. Presentation is often as an abdominal mass (often pulsating) that simulates a tumour. Contrast xray angiography of the abdomen An abdominal aortic aneurysm seen showing an abdominal aneurysm. at autopsy SYPHILLITIC (LEUTIC) ANEURYSM This may involve the ascending aorta in tertiary syphilis (late stage). Syphilitic (luetic) aortitis causes an obliterative endarteritis of the vasa vasorum, leading to ischaemia and smooth-muscle atrophy of the aortic media. Syphilitic aneurysms may dilate the aortic valve ring, causing aortic insufficiency. It may present with respiratory difficulties, feeding difficulties, persistent cou gh, pain cardiac symptoms, rupture Aneurysm of the arch of the aorta which Dissection of the heart and arch of the aorta has eroded through the sternum causing revealing a massive aneurysm. a large pulsatile anterior chest swelling. AORTIC DISSECTION (DISSECTING HAEMATOMA) This is the dissection of blood between and along the laminar planes of the Media with formation of blood filled channels within aortic wall which often rupt ures outward causing massive haemorrhage. Aortic dissection may or may not be associated with marked dilatation of the aorta. For this reason the old term ‗dissecting aneurysm‘ is discouraged. The aetiology usually involves degeneration (cystic medial degeneration) of The tunica media. Aortic dissection presents with severe tearing pain beginning i n the anterior chest and radiating to the back and then moving downwards as the dissection progresses. If there is an aneurysm present, it may compress and obstruct the aortic branches (e.g., renal or coronary arteries). Hypertension and Marfan syndrome are the predisposing factors. It may be iatrogenic and unknown. Thoracic aorta with a dissection Photomicrograph of the aortic wall showing haematoma. blood dissecting along the media.  VASCULITIDES Overview The vasculitides are the various forms of vasculitis. Which is the inflammation of the blood vessels. It is most commonly caused by infectious or immune-mediated mechanisms. Infectious causes of vasculitis include Neisseria, Rickettsiae, and syphilis. Immune-mediated vasculitis occurs due to one of three mechanisms include 1) Immune-complex deposition, 2) ANCA-mediated 3) Direct antibody interaction. In many cases, the pathogenesis of vasculitis is unknown.  VASCULITIDES IMMUNE COMPLEX DEPOSITION–MEDIATED VASCULITIS Mechanism: Antibodies induced by the disease process bind antigens. This interaction forms a complex that deposits within the vessel wall. The immune complex causes vasculitis through activation of complement. Diseases associated with immune complex deposition– mediated vasculitis: Patients with hepatitis B and hepatitis C infections and systemic lupus erythematosus can develop an immune complex deposition–mediated vasculitis. Drug induced vasculitis, which often involves the skin, is due to immune-complex deposition.  VASCULITIDES ANCA-MEDIATED VASCULITIS ANCAs are antineutrophil cytoplasmic antibodies. Mechanism: Unknown for certain; however, one possible explanation is that ANCAs cause degranulation of neutrophils. The degranulation of the neutrophils releases substances that have toxic effects on vessels and surrounding tissue. Two types of ANCA c-ANCA: Antibody against PR-3. p-ANCA: Antibody against myeloperoxidase. Disease associations: Patients with Wegener granulomatosis have c-ANCA. Patients with microscopic polyarteritis and Churg-Strauss syndrome can have p-ANCA.  VASCULITIDES DIRECT ANTIBODY INTERACTION–MEDIATED VASCULITIS Mechanism: Antibodies bind directly to the antigens in the target organ. Disease associations: Goodpasture syndrome, which is caused by antibodies to the glomerular basement membrane, and Kawasaki syndrome, which has anti-endothelial antibodies.  VASCULITIDES CLASSIFICATION OF VASCULITIDES Large Vessel Vasculitis Giant cell / temporal arteritis Takayasu arteritis Medium-sized Vessel Vasculitis Polyarteritis nodosa (pANCA negative) Kawasaki Disease Small Vessel Vasculitis Wegener's Granulomatosis (cANCA positive) Microscopic polyangiitis (pANCA positive) Churg-Strauss (eosinophils, usually pANCA positive) Henoch-Schonlein Cryoglobulinemia Leukocytoclastic vasculitis  VASCULITIDES MAJOR VASCULITIDES Giant cell arteritis, Takayasu arteritis, Polyarteritis nodosa, Wegener granulomatosis, Buerger disease, Kawasaki disease, Microscopic polyarteritis Churg-Strauss syndrome.  VASCULITIDES GIANT CELL ARTERITIS (TEMPORAL ARTERITIS) Vessels affected: Aorta and branches of the carotid arteries such as the ophthalmic and temporal (arteries that run along both sides of your head). Complications: Thoracic aortic aneurysms. Epidemiology: Women older than 50 years of age. Microscopic morphology: Granulomatous inflammation of vessel wall with disruption of elastic lamellae Clinical presentation of giant cell arteritis: Includes visual disturbances (e.g., diplopia and visual loss) and unilateral temporal headache and jaw claudication. Patients can have an elevated erythrocyte sedimentation rate. Diagnosis: Definitive diagnosis requires biopsy. Treatment of giant cell arteritis: Steroid therapy  VASCULITIDES GIANT CELL ARTERITIS (TEMPORAL ARTERITIS)  VASCULITIDES TAKAYASU ARTERITIS Vessels affected: Aorta, branch vessels to upper extremities, and pulmonary arteries. The condition is also called ―pulseless disease.‖ Complications: Thoracic aortic aneurysms. Epidemiology: Women younger than 50 years of age; Asians. Morphology of Takayasu arteritis Gross: Vessel wall with near occlusion of lumen by thick intima. Microscopic: Varies from a mononuclear inflammatory infiltrate to granulomatous inflammation. Intimal proliferation and fibrosis is present.  VASCULITIDES TAKAYASU ARTERITIS Clinical presentation of Takayasu arteritis: Weak pulses in upper extremities; arthralgias, myalgias, night sweats, visual disturbances, and fever. Patients can have an elevated erythrocyte sedimentation rate. Important point: Because giant cell arteritis and Takayasu arteritis can have similar mi croscopic and gross features, the diagnosis is based largely upon epidemiology. Some texts use the term giant cell arteritis to designate both temporal arteritis and Takayasu arteritis, with the two conditions separated by epidemiology and symptoms  VASCULITIDES POLYARTERITIS NODOSA Vessels affected: Small or medium-sized muscular arteries. Polyarteritis nodosa does not involve the smaller vessels (i.e., venules, capillaries, or arterioles) or pulmonary arteries. Commonly involved vessels are the renal and visceral arteries. Epidemiology: Usually young adults. Important point: About 30% of cases are associated with hepatitis B and C infection. Morphology of polyarteritis nodosa Microscopic: Transmural inflammation of vessels in combination with fibrinoid necrosis (i.e., smudgy, pink degeneration of wall), which leads to scarring Important point: Patients have lesions in various stages (i.e.,some inflammation, some scarring); in other words, the lesions are of different ages (referred to as temporally heterogeneous).  VASCULITIDES POLYARTERITIS NODOSA Clinical presentation of polyarteritis nodosa Polyarteritis nodosa presents a challenging clinical diagnosis since a multitude of symptoms are possible. Hypertension and abdominal pain are common. Arthritis and myalgias are present in more than 60% of cases. Polyarteritis nodosa is not associated with glomerulonephritis; however, renal artery involvement is usually prominent and often the cause of death. There is no association with ANCA  Polyarteritis nodosa. Note the prominent fibrinoid necrosis (smudgy eosinophilic changes) of the wall of this vessel and the accompanying inflammatory infiltrate.  VASCULITIDES WEGENER GRANULOMATOSIS Vessels affected: Small vessels in upper and lower respiratory tract and kidney. Microscopic morphology: Granulomatous inflammation. Clinical presentation of Wegener granulomatosis Acute necrotizing granulomas of the upper and lower respiratory tract, causing chronic sinusitis. Necrotizing and granulomatous vasculitis of organs: Most prominently involve the lungs, forming nodules and infiltrates and causing pneumonitis. Focal necrotizing or crescentic glomerulonephritis, causing renal disease.  VASCULITIDES WEGENER GRANULOMATOSIS Important point regarding Wegener granulomatosis: In addition to the above described classic clinical triad, Wegener granulomatosis is also associated with c- ANCA.  VASCULITIDES BUERGER DISEASE (THROMBOANGIITIS OBLITERANS) Vessels affected: Small and medium-sized arteries, most commonly radial and tibial arteries. Epidemiology: More common in Israel, India, and Japan than in the United States. Almost completely limited to cigarette smokers. Pathogenesis of Buerger disease: Unknown, but possibly due to the direct toxic effects of tobacco on vessels or a hypersensitivity reaction to the tobacco products.Increased prevalence of HLA-A9 and HLA-B5 is identified in patients with Buerger disease. Microscopic morphology: Segmental acute and chronic vasculitis; can have thrombosis of the lumen; thrombus can contain microabscesses. Complications of Buerger disease: Ulcers of toes, feet, or fingers. Clinical presentation: Severe pain with activity or rest, most likely due to neural in volvement and digital ulceration.  VASCULITIDES KAWASAKI DISEASE (MUCOCUTANEOUS LYMPH NODE SYNDROME) Vessels affected: Most important is involvement of the coronary arteries. Complications of Kawasaki disease: Includes aneurysms of the coronary arteries an d myocardial infarction. These are late complications occurring many years after acute disease. Microscopic morphology: Similar to polyarteritis nodosa but with less prominent fibrinoid necrosis. Clinical presentation of acute disease: Kawasaki disease classically presents in children younger than 5 years of age who present with a high fever (up to 40°C, or 104°F) for more than 5 days; with conjunctivitis, strawberry tongue, cervical lympha denopathy; and with peeling erythematous rash of lips, palms, and soles of feet.  VASCULITIDES MICROSCOPIC POLYARTERITIS Vessels affected: Smaller vessels than those that are affected by polyarteritis nodosa. Organs involved: Skin, kidney (causing glomerulonephritis), and lungs (causing pulmonary capillaritis). Microscopic morphology of microscopic polyarteritis: Temporally homogeneous lesions. Clinical presentation: Associated with p-ANCA.  VASCULITIDES CHURG-STRAUSS SYNDROME Vessels affected: Small to medium-sized arteries. Microscopic morphology: Granulomatous vasculitis. Clinical presentation: Asthma, eosinophilia, and pulmonary infiltrates.  Thanks for listening ANY QUESTIONS ?