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2 major mechanisms of vascular pathology
1 Narrowing (stenosis) or complete obstruction of vessel lumens, either progressively (e.g., by atherosclerosis) or precipitously (e.g., by thrombosis or embolism);

2 weakening of vessel walls, leading to dilation or rupture.
Three concentric layers of large arteries
1. intima consists of a single layer of endothelial cells with minimal underlying subendothelial connective tissue. seperated from media by internal elastic lamina.

2. Media consists of smooth muscle cells that get their O2 fromd diffusion through the lumen via holes in internal elastic lamina. For thicker media, vasa vasorum supplies outer 1/2-1/3, sperated via the external elastic lamina

3. Adventitia
consisting of connective tissue with nerve fibers and the vasa vasorum.
Three major processes of blood vessel formation and remodeling
1. Vasculogenesis - formed by hemiangioblast precursors that develop into vascular system  VEGF, later remodeling requires pericytes and sm muscle cells ( aniopoietin 1 binding to Tie2 R)

Angiogenesis /neovascularization- constitutes the process of new vessel formation in the mature organism.

Arteriogenesis refers to the remodeling of existing arteries in response to chronic changes in pressure or flow, and results from an interplay of endothelial cell–and smooth muscle cell–derived factors
Congenital Anomalies: Development/ Berry Aneurysms
occur in cerebral vessels; when ruptured these can be causes of fatal intracerebral hemorrhage.
Congenital Anomalies:
Arteriovenous fistulas
- abnormal, typically small, direct connections between arteries and veins that bypass the intervening capillaries,
- can also be caused by rupture of an arterial aneurysm into an adjacent vein, from penetrating injuries that pierce arteries and veins, or from inflammatory necrosis of adjacent vessels; intentionally created arteriovenous fistulas are used to provide vascular access for chronic hemodialysis.
- can cause intracerebral hemorrhage and High output cardiac failue
Congenital Anomalies:
Fibromuscular dysplasia
- focal irregular thickening of the walls of medium and large muscular arteries, including renal, carotid, splanchnic, and vertebral vessels,thickened by a combination of irregular medial and intimal hyperplasia and fibrosis
-  High risk for 1st degree relatives + young women
- can cause renovascular HTN, aneurysms,
Endothelial cells
Structure Buzzwords
Functions (8)
- Weibel-Palade bodies- intracellular membrane-bound storage organelles for von Willebrand's factor,can be id by IHC
- Functions
1- maint of permeability barrier

2- elaboration of anticoagulant, antithrombotic, fibrinolric regulators
(prostacyclin, thrombomodulin, heparin like molecules, plasminogen activator )

3- elaboration of prothrombotic molecules ( vWF, Tissue factor, Plasminogen activator inhibitor)

4- ECM production (collagen, proteoglycans)

5- Modulation of Blood flow and vasc reactivity ( vasoconstrictors: endothelin + ACE, vasodilators : NO prostacyclin)

6-regulation of inflammation + immunity (IL1, IL-6 chemokines, adhesion: VCAM1, ICAM, E selectin, P selectin, Histocompatibility ags)

7- regulation of cell growth ( growth stim : PDGF, CSF, FGF Grotwth inhibitors : heparin, TGF B)

8- Oxidation of LDL
Endothelial Activation
caused by
leads to
Def - Structurally intact endothelial cells can respond to various pathophysiologic stimuli by adjusting their usual (constitutive) functions and by expressing newly acquired (inducible) properties

caused by normotension,laminar flow, GF(VEGF),cytokines, hpoxia and acidosis

leads to GFs, vasoactive mediators, adhesion molecules, anticoagulants
Endothelial dysfunction
Caused by
Leads to
- Def = altered phenotype that impairs vasoreactivity or induces a surface that is thrombogenic or abnormally adhesive to inflammatory cells.

- caused by : turbulent flow, HTN, cytokines, complement, bacterial products, lipid products, advanced glycation end produsts, hypoxia acidosis , viruses, cigarette smoke

- leads to GF, chemokines, cytokines, procoagulant proteins , adhesion molecules , vasoactive molecules
Vascular smooth muscle

1- proliferate when appropriately stimulated
2 - synthesize ECM collagen, elastin, and proteoglycans
3- elaborate growth factors and cytokines
4- Vasoconstriction/Vasodilation

Promoters: PDGF,endothelin-1, thrombin, FGF, IFN-γ, IL-1

Inhibitors: heparan sulfates, nitric oxide &TGF-β
Intimal Thickening

neointimal smooth muscle cells
Vascular injury—with endothelial cell loss or even just dysfxn —stimulates sm muscle cell growth and assoc matrix synthesis that thickens the intima= response of the vessel wall to any insult.

MOA : Recruitment of sm muscle cells from circulating precursors/media. Sm muscle proliferation + elaboration of ECM in intima

Neointimal smooth muscle cells - do not contract like medial sm muscle, but have capacity to divide

Promoters- PDGF, endothelin-1, thrombin, FGF, IFN-γ, and IL-1

Inhibitors - heparan sulfates, nitric oxide, and TGF-β

Physio- can return to nonproliferative state but thickening is permanent, can see nonsignificant intimal thickening in aging process bc compensatory outward remodeling of the vessel results in little net change in the luminal diameter
Causes of Secondary HTN
Renal (6)
Endocrine (7)
Cardiovasc (5)
Renal = Acute GN, CKD, Polycystic diseas, RAS, Renal vasculitis, Renin-producing tumors

Endocrine = adrenocortical hyperfxn ( cushings,  hyperaldo, congenital adrenal hyperplasia, licorice), exogenous hormones ( glucocor, estrogen( pregnancy/oral contraceptives, MAO I, sympathomimetics), pheo, acromegaly, hypothyroidism, hyperthyroidism, pregnancy induced

CV= coarctation of aorta, polyarteritis nodosa, increased intrvasc volume, incr CO, aortic rigidity

Neuro= psychogenic, increasd intracranial P, sleep apnea, acute stress
Vascular Pathology in HTN

Morphology changes (2)
1. Hyaline arteriolosclerosis - homo, pink hyaline thickening with associated luminal narrowing. plasma protein leakage across injured endo cells, and incr sm muscle cell matrix synth in response to chronic hemodynamic stress. common in elederly,diabetic microangiopathy ( in nephroscleorosis this causes glom scarring )

2.Hyperplastic arteriosclerosis - in malignant HTN , onion skin lesions,smooth muscle cells with thickened, reduplicated basement membranes. ( + fibrinoid necrosis/ necrotizing arteriolitis in kidney)

3 types
Def - arterial wall thickening and loss of elasticity

3 types
1. Arteriosclerosis - small arteries and arterioles, downstream ischemia , hyaline/hyperplastic  

2. Mönckeberg medial sclerosis- >50y old,calcific deposits in muscular arteries may under go metaplastic change to bone, not clin significant bc they do not occlude lumen

3. Atherosclerosis - hardening.
Risk Factors for Atherosclerosis
Modifiable (5)
Nonmodifiable- increasing age, male gender family history, genetic abnormalities

Modifiable - hyperlipidemia,HTN , cig smoking, diabetes, C reactive protein
Modifiable Risk factors
- Hyperlipidemia
- Cigarette smoking
- Diabates Mellitus
- Hyper lipidemia/ hypercholesterolemia , major factor is LDL( form of cholesterol delivered to tissues) vs HDL(  moves cholesterol to liver for excr in bile). Diets saturated = badd, polyunstarurated = good ,
statins are a class of drugs to use to inhibit hydroxymethylglutrayl coenzyme A(HMG-CoA) reductase rate limiting step in heptaic cholesterol synth

- HTN - both systolic & diastolic is important , increases risk of IHD by 60% alone, most imp cause of LVH

-smoking - rsik factor for men + rising in women , doubles death rate from IHD

- Diabetes - MI chances double, increased risk of strokes  + 100x risk of increased risk of atherosclerosisinduced gangrene
20% of CV events occur in the absence of HTN, hyperlipidemia, smoking or diabetes. Other factors such as :
- Inflammation
- Hyperhomocysteinemia
- Metabolic syndrome
- Lipoprotein
- Hemostasis
- Inflammation - resent during all stages of atherogenesis and is intimately linked with atherosclerotic plaque formation and rupture.C-reactive protein (CRP) has emerged as one of the simplest and most sensitive,acute-phase reactant synth by liver.innate immune response by opsonizing bacteria and activating complement,activate local endothelial cells and induce a prothrombotic state and also increase the adhesiveness of endothelium for leukocytes, predicts the risk of myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death

- Hyperhomocysteinemia- connection to coronary artery disease, peripheral vascular disease, stroke, and venous thrombosis, can be caused by low folate and vitamin B12 intake, and inborn errors if metabolism causing early vasc disease

- Metabolic syndrome- insulin resistance ,HTN and central obesity.Dyslipidemia leads to endo cell dysfxn secondary to increased oxidative stress; there is also a systemic proinflammatory state that predisposes to vascular thrombosis.

- Lipoprotein- form of LDL that contains the apolipoprotein B-100 portion of LDL linked to apolipoprotein A. Lipoprotein (a) levels are associated with coronary and cerebrovascular disease risk, independent of total cholesterol or LDL levels

- Hemostasis- Thrombin, through both its procoagulant and proinflammatory effects, as well as platelet-derived factors both are increasingly recognized as major contributors to local vascular pathology.

-Misc. - lack of exercise; competitive, stressful life style (“type A” personality); and obesity (which is often associated with hypertension, diabetes, hypertriglyceridemia, and decreased HDL).
Pathogenesis of Atherosclerosis
- Response to injury hypothesis
Definition - atherosclerosis as a chronic inflammatory and healing response of the arterial wall to endothelial injury. Lesion progression occurs through the interaction of modified lipoproteins, monocyte-derived macrophages, and T lymphocytes with the normal cellular constituents of the arterial wall
Atherosclerosis is produced by  the following
1.Endothelial inury -
2. Accum of lipoproteins
3.Monocyte adhesion to endothelium
4. Platelet adhesion
5. Factor release
6. Sm muslce prolif/ ECM production
7. Lipid accum extracellular+ intracellular
Endothelial Injury
MC causes (2)
vasc permeability + leuko adhesion + thrombosis by dysfunctional edothelial cells  = intimal thickening @
MC causes are
1. hemodynamic disturbances - turbulence is really imp bc plaques tend to occur at ostia of exiting vessels , bracnh points and post wall of abd aorta. Laminar flow induces expression of antioxidant superoxide dismutase etc ( atheroprotective genes)
2. hypercholestrolemia = dominant lipids in atheromatous plaques are cholesterol and cholesterol esters,homozygous familial hypercholesterolemia, caused by defective LDL receptors and inadequate hepatic LDL uptake  can lead to MI  before age 20 years,severity of atherosclerosis tracks with plasma cholesterol /LDL

MOA : increasing local oxygen free radical production; oxygen free radicals can injure tissues and accelerate nitric oxide decay, reducing its vasodilator activity. lipoproteins accumulate within the intima. These lipids are oxidized through the action of oxygen free radicals locally generated by macrophages or endothelial cells., oxidized LDL is ingested by macrophages through a scavenger receptor = foam cells , oxidized LDLs = release of growth factors, cytokines, and chemokines by endo cells , also LDL is cytotoxic to endo cells
Endothelial injury via Inflammation
dysfunctional arterial endothelial cells express adhesion molecules that encourage leukocyte adhesion; vascular cell adhesion molecule 1 (VCAM-1), in particular, binds monocytes and T cells- migrate into intima and produce chemokines

Monocytes --> macrophages and engulf lipoprotein + oxidized LDL, protective but the oxidized LDL  causes prod of cytokines (TNF + MCF1 )= recruitment  of other cells and also induce production of ROS

T lymphocytes --> interact w/ macrophages = chronic inflammatory state--> inflammatory cytokines IFN gamma,

this inflammatory state --> atcivated leukocytes + vasc wall release of GF + sm muscle prolif + ECM synth

Endothelial injury via infection
not proven yet
Herpesvirus, cytomegalovirus, and Chlamydia pneumoniae have all been detected in atherosclerotic plaques but not in normal arteries, and seroepidemiologic studies find increased antibody titers to C. pneumoniae in patients with more severe atherosclerosis.--> infect sites of early atheroma formation; their foreign antigens could potentiate atherogenesis by driving local immune responses, or infectious agents could contribute to the local prothrombotic state
Endothelial injury via Smooth Muscle Proliferation
Sm muscle cell prolif + ECM deposition  convert a fatty streak ---> mature arethoma

Several growth factors are implicated: PDGF (released by locally adherent platelets, as well as macrophages, endothelial cells, and smooth muscle cells), FGF, and TGF-α. The recruited smooth muscle cells synthesize ECM (notably collagen) that stabilizes atherosclerotic plaques. However, activated inflammatory cells in atheromas can cause intimal smooth muscle cell apoptosis, and also increase ECM catabolism resulting in unstable plaques .
Morphology of Atherosclerosis
Fatty streak
Atherosclerotic Plaque
Components of plaques (3)
can lead to
-Fatty streak= lipid filled foamy macrophages, mutiple minute  flat yellow spots --> elongated 1 cm streak. seen in children <1y and in all children >10 y

-Atherosclerotic Plaque- intimal thickening and lipid accumulation , white to yellow w superimposed thrombus which is red-brown, patchy and eccentric
lower abd aorta> thoracic aorta
lower abdominal aorta>coronary arteries>popliteal arteries> internal carotid arteries >the circle of Willis.
rarely in UE, mesenteria and renal ,(except at ostia), lesions are at various stages

-Components of plaques (3)
1.cells, including smooth muscle cells, macrophages, and T cells
2.ECM, including collagen, elastic fibers, and proteoglycans
3.intracellular and extracellular lipid
they have superficial fibrous cap w/ sm muscle cells + collagen , shoulders have macrophages + T cells and sm muscle cells
Necrotic core = cholesterol, lipid laden macrophages , fibrin and thrombus plasma prots + empty clefts  + calcification of aarethoma can occur
Fibrous plaque = onl sm muscle cells + fibrous tissue

can lead to-
1.rupture/ulceration/erosion =exposes blood to highly thormbotic substances = thrombosis --> ischemia
2. hemorrhage into plaque = rupture of fibrous cap or neovasc --> contained hematoma --> expand the plaque and induce plaque rupture
3.Atheroembolism -->Plaque rupture can discharge atherosclerotic debris into the bloodstream, producing microemboli.
4. aneurysm  formation --> atherosclerosis  induced pressure/ischemic atrophy of underlying media , w loss of of elastic tissue --> causes weakness --> enurysmal dilation and potential rupture
Consequences of Atherosclerosis
-Large elastic arteries (e.g., the aorta, carotid, and iliac arteries) and large and medium-sized muscular arteries (e.g., coronary and popliteal arteries) are the major targets of atherosclerosis.

mural thrombosis, embolization + wall weakening --> anuerysm + rupture

plaque rupture, plaque eerosion , plaque hemorrhage, mural thrombosis , embolization --> occlusion by thrombus
progressive plaque growth --> critical stenosis
Atheroslcerotic stenosis
in small arteries, early changes include outward remodeling of vessel media to preserve diameter,
critical stenosis - demand> flow
70% in angina pts (stable angina after exercise)
other complications :mesenteric occlusion and bowel ischemia, chronic IHD, ischemic encephalopathy, and intermittent claudication
Acute Plaque change

Vulnerable Plaque vs Stable Plaque
erosion/rupture is followed by partial /complete vasc thrombosis. 3 types
1. rupture/fissuring - exposing highly thrombogenic plaque contituents
2.erosion/ulceration -exposing the thrombogenic subendothelial basement membrane to blood
3. Hemorrhage into the atheroma, expanding its volume

the majority of plaques that undergo abrupt disruption and coronary occlusion previously showed only mild to moderate luminal stenosis

vulnerable plaque = large areas of foam cells and extracellular lipid, and those in which the fibrous caps are thin or contain few smooth muscle cells or have clusters of inflammatory cells
stable plaque = thick fibrous cap

major component of cap = collagen, matrix metalloproteinases control collagen turnover

statins may actually relieve plaque inflammation

most serious form, thrombus superimposed on a disrupted but previously only partially stenotic plaque converts it to a total occlusion
Mural thrombus in a coronary artery can also embolize  + multiple growth-related signals in smooth muscle cells

vasoconstriction= is stimulated by (1) circulating adrenergic agonists, (2) locally released platelet contents, (3) impaired secretion of endothelial cell relaxing factors (nitric oxide) relative to contracting factors (endothelin) as a result of endothelial cell dysfunction, and possibly (4) mediators released from perivascular inflammatory cells

Aneurysm definition
An aneurysm is a localized abnormal dilation of a blood vessel or the heart( acquired/congenital) true aneurysm =saccular / intact attenuated arterial wall or thinned ventricular wall of the heart, circumferntial dilation =fusiform
exmples :Atherosclerotic, syphilitic, and congenital vascular aneurysms, and ventricular aneurysms that follow transmural MI

False aneurysm - a defect in the vascular wall leading to an extravascular hematoma that freely communicates with the intravascular space (“pulsating hematoma”)
examples: a ventricular rupture after MI that is contained by a pericardial adhesion, or a leak at the sutured junction of a vascular graft with a natural artery.

Arterial dissection :blood enters the arterial wall itself, as a hematoma dissecting between its layers

all carry risk of rupture MC  risk factors  for aortic aneurysms = atherosclerosis (abd aorta) + HTN (asc aorta)
intrinsic quality of vasc wall connective tissue is poor
Marfan Syndrome - defective synthesis of the scaffolding protein fibrillin leads to aberrant TGF-β activity and progressive weakening of elastic tissue; in the aorta, the consequence is progressive dilation due to remodeling of the inelastic media

Loeys-Dietz - mutations in TGF-β receptors lead to abnormalities in elastin and collagen I and III. Aneurysms in such individuals can rupture fairly easily (even at small size

Ehlers-Danlos syndrome - Weak vessel walls due to defective type III collagen synthesis

Nutritional - altered collagen cross-linking associated with vitamin C (ascorbate) deficiency

defective synthesis of the scaffolding protein fibrillin leads to aberrant TGF-β activity and progressive weakening of elastic tissue; in the aorta, the consequence is progressive dilation due to remodeling of the inelastic media
Balance of collagen synth and degradation is changed by loacl inflammatory infiltr. and destr enzymes
Increased MMP production - by macrophages in atherosclerotic plaque or in vasculitis, probably contributes to aneurysm development[56]; these enzymes have the capacity to degrade virtually all components of the ECM in the arterial wall (collagens, elastin, proteoglycans, laminin, fibronectin).

Decreased tissue inhibitor of metalloproteinase (TIMP) expression=overall ECM degradation

vascular wall is weakened through loss of smooth muscle cells or the inappropriate synthesis of noncollagenous or nonelastic ECM
Ischemia of the inner media occurs with plaque bc of distance O2 has to travel

Systemic HTN = narrowing of vasa vasorum = outer medial ischemia

Ischemia = degenertaive changes  where loss of sm muscle cells or change to scarring and lossof elastic fibers and low ECM synth and production of amorphous ground stubstance (GAGs),= cystic medial degeneration
Mycotic aneurysms
originate (1) from embolization of a septic embolus, 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.

3o sphilis aortic aneurysms, obliterative endarteritis = predilection for small vessels, including those of the vasa vasorum of the thoracic aorta. This leads to ischemic injury of the aortic media and aneurysmal dilation, which sometimes involves the aortic valve annulus. most pts dies of HF by aortic valvular incompetence
Abdominal Aortic Aneurysm
causes and facts
assoc with atherosclerosis in intima  compresses medial and comprimises nutrient/waste diffusion --> media  undergoas necrosis --> wall thinning. increased MMP also plays role

Morphology-  usually below renal a nd before bifurcation , saccular/fusiform , intima shows severe uneven atherosclerosis, bland, laminated, poorly organized mural thrombus that may fill some or all of the dilated segment. can cause smaller aneurysms of iliac arteries

Inflammatory AAAs- dense periaortic fibrosis containing abundant lymphoplasmacytic inflammation with many macrophages and often giant cells
Mycotic - lesions that have become infected by the lodging of circulating microorganisms in the wall, particularly in bacteremia from a primary Salmonella gastroenteritis. In such cases suppuration further destroys the media, potentiating rapid dilation and rupture.

Clinical -  rupture into peritoneal cavity /retroperitoneal tissues w/ massive hemorrhage, obstr of a branch vessel w downstreaminjury , iliac = leg, renal = kidney , mesenteric = GI  vertebral = spinal cord, embolism from artehoma or mural thrombus , impingement on adj struct  presentation as an abd mass

risk based on size <4cm = no risk , 1% 4-5 cm , 11% 5-6cm , 25% >6cm  TX wi surgery

Thoracic Aortic Aneurysms
commonly assoc w/HTN , other causes Marfan , Loeys- Dietz etc

Signs and symptoms
- encorachment on mediatsinal struc
- resp difficulties bc encoroachment on lungs + airways
- difficulty swallowing  due to compression of esophagus
- persistent cough due to irritation or pressure on recurrent laryngeal nerve
- pain cuased by erosison of bones
- cardiac disease as aortic aneurysm --> aortic valve dilation
- rupture
Aortic Dissection
occus when blood splays apart the the laminar planes of media to form a blood filled channel within aortic channel --> can hemorrhage into adj areas

occurs primarily in
1. men from 40-60 with HTN
2. younger pts w// loacalized bn of conn tissue, affecting aorta
also pregnancy ,iatrogenic
but dissection is rare w/ lots of atherosclerosis + medial scarring, medial fibrosis inhibits dissecting hematoma

Pathogenesis - pressure related mech injury/ ischemia due to low flow throgh vasa vasorum. cause unknown  Intramural hematoma w/o intimal tear bc of disruption of vasa vasorum

Morphology- most freq preexisting histo lesion -  cystic medial degeneration , no in flammation
usually initiates w/ intimal tear, transverse/oblique tear  withs harp ragged edges , usually between middle and outer thirds, csan hemorrhage into abd cavities or through percardial sac (cardiac tamponade)
sometimes 2nd distal intimal tear = double barrelled aorta /false channel

most seriosu complications involve dissection  from aortic valve to arch

Proxmal lesions aka Type A dissections (deBaey Type I and II) either just or both ascending and descending aorta

Distal aka Type B  dissections or DeBaey Type III

pain from chest to back  between scapulae, confused w MI , MC cause of death is dissection outwwards into pericardial, pleural or peritoneal cavities. common clinical manifestations include cardiac tamponade, aortic insufficiency, and myocardial infarction or extension of the dissection into the great arteries of the neck or into the coronary, renal, mesenteric, or iliac arteries, causing critical vascular obstruction and associated ischemic consequences; compression of spinal arteries may cause transverse myelitis
Large vessel vascultis
Medium Vessel Vasculitis
Small Vessel Vasculitis

vessel wall inflammation. constitutional signs and symptoms such as fever, myalgias, arthralgias, and malaise. most vasculitides involve small vessels, from arterioles to capillaries to venules

Large vessel vascultis -
Aorta and large branches to extremities, head, and neck

Giant-cell (temporal) arteritis- Granulomatous inflammation; frequently involves the temporal artery, >50 y old + polmyalsgia rheumatica
Takayasu arteritis- Granulomatous inflammation < 50 y old

Medium Vessel Vasculitis-
Main visceral arteries and their branches
Polyarteritis nodosa- Necrotizing inflammation in renal arteries but not  pulmonary vessels
Kawasaki disease - Arteritis with mucocutaneous lymph node syndrome, in children, coronary a can be involved with aneurysm/ thrombosis

Small Vessel Vasculitis- Arterioles, venules, capillaries, & small arteries
Wegener granulomatosis- Granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small vessels, including glomerular vessels. Associated with PR3-ANCAs
Churg-Strauss syndrome Eosinophil-rich granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small vessels. Associated with asthma and blood eosinophilia. Associated with MPO-ANCAs.
Microscopic polyangiitis Necrotizing small-vessel vasculitis with few or no immune deposits; necrotizing arteritis of small and medium-sized arteries can occur. Necrotizing glomerulonephritis and pulmonary capillaritis are common. Associated with MPO-ANCAs.
Giant Cell (temporal) Arteritis

Mc form of vascultis in elder ly inUSA + Europe, chronic, typically granulomatous inflammation of large to small-sized arteries, can also involve veretra and opthalmic arteries(permanent blindness), medical emergency

- initial T cell mediated immune response , pro inflammator cytokines like TNF and enti-endothelial cell humaoral immune responses also involved.
Certain HLA II haplotypes , therapeutic response to steroids

Involved arterial segments develop nodular intimal thickening (with occasional thromboses) that reduces the lumenal diameter. Classic lesions exhibit medial granulomatous inflammation that leads to elastic lamina fragmentation; there is an infiltrate of T cells (CD4+> CD8+) and macrophages. healed stage is marked by medial scarring and intimal thickening

Clinical features
rare before 50 y, fever, fatigue, weight loss—or include facial pain or headache that is most intense along the course of the superficial temporal artery, which can be painful to palpation, occurs in 50% of pateints (diplopia to complete vsion loss), test not exclusive, corticosteroids

Takayasu Arteritis

granulomatous vasculitis
of medium and larger arteries characterized principally by ocular disturbances and marked weakening of the pulses in the upper extremities (hence, its other name, pulseless disease).

transmural fibrous thickening of the aorta—particularly the aortic arch and great vessels, Those over 50 years of age are designated as having giant-cell aortitis, while those under 50 have Takayasu aortitis

Morphology - involves aortic arch,50% of pts involved with pulm symptoms , intimal hyperplasia , weakness of per pulses bc of stenosis of great vessels

histologically indistinguishable from  of giant-cell temporal infiltrates- in all three layers of blood vessels , aortic root causes aortic insufficiency

Clinical- fatigue, weight loss, and fever. With progression, vascular symptoms appear and dominate the clinical picture, including reduced blood pressure and weaker pulses in the upper extremities; ocular disturbances, including visual defects, retinal hemorrhages, and total blindness; and neurologic deficits,
possible : claudication of the legs, pulm HTN, MI, systemic HTN( renal involvement), long term survival w/some visual/neuro deificts


typically involving renal and visceral vessels but sparing the pulmonary circulation, no assoc w/ANCAs , 30% of pts with PAN have HBV. etilogy unknown

Morphology - segmental transmural necrotizing inflammation ofsmall to medium-sized arteries, weakens the arterial wall, and impaired perfusions , acute pahse = transmural inflammation + fibrinoid necrosis, later = fibrous (occasionally nodular) thickening of the vessel wall that can extend into the adventitia. Characteristically, all stages of activity (from early to late) coexist in different vessels or even within the same vessel, suggesting ongoing and recurrent insults.

Clinical features :oung adults , may be acute, subacute or chronic,  long smptom free intervals
fibrous (occasionally nodular) thickening of the vessel wall that can extend into the adventitia. Characteristically, all stages of activity (from early to late) coexist in different vessels or even within the same vessel, suggesting ongoing and recurrent insults.

Kawasaki disease
MC heart acquired disease in children, acute febrile usually self limited illness of infancy , can involve coronary artery, thought to result from a delayed-type hypersensitivity reaction of T cells to an as yet uncharacterized antigen. This leads to cytokine production and macrophage activation, and is accompanied by polyclonal B-cell activation, see autoabs to endo cells and sm muscle cells

Morphology - pronounced inflammation affecting entire thickness of vessel wall , healed lesions may have obstructive intimal thickening
Clinical - aka mucocutaneous lymph node syndrome, 20% have CV sequelae
Microscopic polyangitis (aka hypersensitivity vasculitis or leukocytoclastic vasculitis.)

necrotizing vasculitis that generally affects capillaries, as well as arterioles and venules
of a size smaller than those involved in polyarteritis nodosa lesions same age in any given pt (vs PAN)
pulm are normally affected ( this can be presentation (HSP, essential mixed cryoglobinuria etc)

ab response to antigens , may be immune complex deposition +  may trigger 2nd ry immune repsonse s (pANCAs), most lesions do not have immune complexes (MPO ANCAs are starting to be implicated)

Morphology : segmental fibrinoid necrosis  w/ fibrinoid necrotizng lesions, esemble polyarteritis nodosa but typically spare medium-sized and larger arteries; consequentlypost-capillary venules), only infiltrating and fragmenting neutrophils are seen, giving rise to the term leukocytoclastic vasculitis , can be pauci immune
Clinical : depends on vasc bed major clin symptoms :
hemoptysis; hematuria, and proteinuria; bowel pain or bleeding; muscle pain or weakness; and palpable cutaneous purpura
Tx with steroid immunosuppression

Churg Strauss syndrome ( aka allergic granulomatosis and angiitis)

small-vessel necrotizing vasculitis classically associated with asthma, allergic rhinitis, lung infiltrates, peripheral hypereosinophilia, and extravascular necrotizing granulomas
palpable purpura), gastrointestinal tract bleeding, and renal disease (primarily as focal and segmental glomerulosclerosis) are the major associations, Myocardial infiltrates of eosinophils and cytotoxicity= 1/2 the deaths

Patho :hyper-responsiveness to an allergic stimulus; in asthmatics, leukotriene receptor antagonists are reported as a trigger

Triad of :
acute necrotizing granulomas of upper/lower resp tract, necrotizing or granulomatous vasculitis  (small-med sized arteries), renal disease w/ focal necrotizing , often crescenting  GN

Pathogenesis - cell–mediated hypersensitivity reaction, possibly to an inhaled infectious or other environmental agent; such a pathogenesis is supported by the presence of granulomas and a dramatic response to immunosuppressive therapy. PR3-ANCAs are present in up to 95% of cases; they are a useful marker of disease activity and may participate in disease pathogenesis.

Morphology : sharply segemented acute and chronic vasculitis of medium sized and small arteries (extremeties), thrombus contains small miscroabscesses. Thrombus may reorganize and recanalize + extend into contig veins and nerves ( vs other vascilitis which becomes encased with fibrous tissue)

Clinical Features
superficial nodular phlebitis, cold sensitivity of Raynaud phenomenon in the hands and  instep claudication

vs atherosclerosis buerger's has sever pain even in rest

absitinence from smoking
Vasculitis assoc with other disorders

Class PAN/ hypersensitivity angitis  sometimes assoc w/ other disorders , such as rheumatoid arthritis, SLE, cancer or systemic illnesses such as essential cryoglobulnuria antiphospholipid antibody syndrome, and Henoch-Schönlein purpura.

Rheumatoid vasculitis - after chronic RA, lead to visceral infarction and sometimes  aortitis

diff is important for ex.  calssic immune complex lupus vasculitis and antiphospholipid ab syndrome are morphologically similar ,but antiimflammatory therapy is only for  the former and anticoagulant therpay is for the latter
Infectious vasculitis

direct invasion of infectious agents, usually bacteria or fungi ( Aspergillus and Mucor)
can be part of a localized tissue infection ( bacterial pneumo + abcesses ) or less commonly it can arise from hematogenous seeding of bacteria during septicemia/ embolization from sepsis of infective endocarditis

vasc infection = weaken arterial walls and culm in mycotic aneuryms/ induce thrombosis and infarction

inflammation-induced thrombosis of mening. vessels in bacterial meningitis can cause infarction of brain.
Raynaud phenomenon

results from exaggerated vasoconstriction of digital arteries and arterioles = paroxysmal pallor or cyanosis of the digits of the hands/feet, red, white, and blue color changes from most proximal to most distal, correlating with proximal vasodilation, central vasoconstriction, and more distal cyanosis

Primary Raynaud phenomenon - exxageration of local vasomotor responses to cold/emotional stresses, mostly young women , intimal thickenning later in disease, usually benign but can cause atrophy of skin , subQ tissues and muscles , ulceration and ischemic gangrene are rare

Secondary raynaud phenomenon- vascular insufficienc of extremities to arterial disease cuased by SLE, scleroderma, Buerger disease  or even atherosclerosis , raynaud may be first symptom of these diseases evaluation is necessary but only 10% will have underlying disease 
Varicose veins

abnormally dilated, tortuous veins produced by prolonged increased intraluminal  pressure and loss of vessel wall support , superficial veins  of upper + lower leg usually involved, 10x normal venous Pressure --> venous stasis and pedal edema ( simple orthostatic edema
Risk factors : obesioty, female, pregnancy, familial in some cases.

- renders venous valves incompetent and leads to stasis, congestion edema, pain and thrombosis , persistent edema and ischemic skin changes  ex stasis dermatitis, embolism from superficial veins very rare (vs DVT)

Esophageal varices - liver cirrhosis ( portal vein obstr/ hepatic vein thrombosis)= causes portal vein HTN. Portal HTN opening of porto systemic shunts that increase blood flow at gastroesophageal jxn( esophageal varices), the rectum ( forming hemorrhoids) and periumbilical veins  of abdominal wall ( caput medusa)--> RUPTURE can lead to massive/fatal GI bleed

Hemorrhoids - primary varicose dilation at venous plexus at anorectal jxn ( prolonged pelvic vasc congestion due to pregnancy / chronic constipation Hemorrhoids are uncomfortable and may be a source of bleeding; they can also thrombose and get inflamed, and are prone to painful ulceration
Lymphangitis and Lymphedema

Primary are very rare , usually secondary w/ inflmmation or malignancies

Lymphangitis - acute inflammation elicited when bacterial infections spread into lymphatics; the most common agents are group A β-hemolytic streptococci,dilated and filled with an exudate of neutrophils and monocytes;--> produce cellulitis or focal abscesses

red painful subcutaneous streaks and painful enlargement of draining lymph nodes, can spread to veins  causing sepsis

Primary lymphedema - isolated congenital defect/ familial Milroy disease= lymphoid agenesis hypoplasia , secondary is from blockage  from
malignant tumors, surg procedures, post irradiation fibrosis , filariasis, post inflammatory thrombosis and scarring

- increases P in lymphatics and causes fluid accum., persistence of edema causes deposition of interstitial connective tissue , rawny induration or peau dorange  apeearance of overling skin , and eventually ulcers due to inadequate tissue perfusion
Milky accum of lymph in various spaces = chylous ascites ( abdomen), chylothorax and chylopericardium  cuased by rupture of dilated lymphatics , obstructed by infiltr  tumor mass
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