--BV walls are made up of intima/endothelial cells, media/smooth muscle cells, and adventitia/extracellular matrix. The intima is a single layer of sensitive endothelial cells (EC's) with some elastic CT but not much sub-endothelial CT. The intima naturally thickens with age but if it thickens too far it is pathological. The smooth muscle cells of the media are known as SMC's from this point forward, and they get their nutrients from diffusion from the lumen or form the vaso vasorum depending on location. And adventitia is the CT, nerves and vaso vasorum that surround the vessels.

Arteries
--categorized by size: large elastic > medium muscular > small arteries > arterioles
--can be told from each other not just by size but by the content of their walls
--large elastic have lots of elastin (visible ruffled line)
--medium muscular have lots of SMC's which control the lumen size and hence blood flow
--small arteries and arterioles also change size readily to control blood flow
--capillaries are where exchange takes place, and they can be quite specialized

Endothelial cells = EC's
--semi-permeable membrane controls transfer of large mols
--high blood pressure, histamine and inflam affect permeability
--differ by anatomical site and adaptation to local environment
--constitutive vs inducible properties: damages due to cytokines, bacterial products (ROS, Chlamydia pneumonia in white men), hemodynamic forces, lipid products, advanced glycosylation end products, viruses (CMV, HSV), complement products and hypoxia can cause the induction of genes and induce adhesion molecules, cytokines, chemokines, growth factors, vasoactive mediators, pro- and anti-coagulation proteins, MHC molcules and more
--endothelial injury hypothesis: injury to EC's-->increased permeability and adhesion-->lipids, monocytes and platelets adhere to EC's-->monocytes enter inima, change to macrophages and become foam cells-->aggregated platelets and such produce PDGF, FGF, TGF-alpha-->SMC's proliferate and migrate into intima-->extracellular matrix forms in intima which accumulates collagen and proteoglycans, maturing the fibro-fatty plaque and constrict the lumen

ARTERIOSCLEROSIS = hardening of the arteries
--atherosclerosis = most frequent and important, intimal thickening and lipid deposition in elastic and muscular arteries, individual plaques are atheromas (athero = porridge-like)
--Mockenberg medial calcific sclerosis = medial sclerosis = calcific deposits on muscular arteries
--arteriosclerosis = small arteries and arterioles have hyaline thickening
--clinicopathological effects: fixed atherosclerotic plaques, narrowing of epicardial coronary arteries, intraluminal thrombosis overlying a disrupted atherosclerotic plaque, platelet aggregation, vasospasm

ATHEROSCLEROSIS
--intima thickens and lipid deposition in elastic and muscular arteries
--develop mainly in elastic arteries, large & medium sized muscular arteries
--seen in heart, brain, kidneys, lower extremities
--athero = porridge-like
--SIX TYPES:
I: fatty dots (isolated foam cells) due to lipid accumulation start in childhood clinically silent
II: fatty streaks dt lipids, start in childhood, clinically silent
III: intermediate lesions grow by lipid accumulation, begin in 30's, clinically silent
IV: atheromas grow by lipid accumulation, begin in 30's, may show symptoms
V: fibroatheromas show accelerated SMC and collagen in intima, begin in 40's, may show symptoms
VI: complete complicated lesions grow by thrombosis, hematoma from 40's, may show symptoms
--consequences: MI, cerebral infarction, aortic aneurism, peripheral vascular dz
--advanced lesions-->focal rupture, ulceration or erosion of luminal surface of atheromatous plaues may result in exposure of highly thrombogenic substances-->discharge of debris into bloodstream
--hemorrhage into a plaque may be intiiated by rupture of either the overlying fibrous cap or the thin-wall capillaries that vascularize the plaque. A contained hematoma may expand the plaque or induce plaque rupture.
--Thrombosis usu occurs on disruped lesions (ruptured, ulcerated, eroded, hermorrhaged) and may paritally or completely occlude the lumen. Thrombi may heal and add to the existing intimal plaque.
--aneurysmal dilation may occur dt atrophy of underlying media w/ loss of elastic tissue-->potential rupture

RISK FACTORS FOR ATHEROSCLEROSIS
--age, maleness when under 50, family hx, genetics, HTN, cigs, DM, homocysteine, alcohol, trans fat intake, lipoprotein a, obesity
--hypothyroidism, syndrome x, increased GH, hyperuricemia, hyperlipidemia, hyperadrenalism
--monkeys at bottom of social group more prone to AS
--"hot reactors" with high sympathetic activity in response to stress more at risk
--perception of negative relationship with parents assoc with 2x risk of CAD
--cigs contain aryl hydrocarbons (benzypyrene, methylcholanthrene) that damage and are carcinogenic to EC's, smokers have a 3-5x increase in CAD compared to nonsmokers
--women over 35 who smoke and take oral contraceptives have the highest risk of all!!
--HFCS = high fructose corn syrup--> hyperuricemia --> increased risk
--DM --> 2x MI risk
--age: between age 40 and 60 the risk of MI increases 5x
--gender: incidence in women catches up with men after menopause, equal 70-80
--hyperlipidemia: ratio of LDL to HDL matters, adjust w/ omega 3's, exercise, avoid alc
--statins: inhibit HMG CoA reductase enzyme used by liver for cholesterol synthesis
--homocystinuria: hyper can be hereditary, correlation to coronary artery dz (CAD) and peripheral vascular dz (PVD)
--multiple infections increases the risk of atherosclerosis: gingivitis, heat shock proteins not good sign
--lack of physical activity-->increased risk
--eating fried food (YUM)
--sugary diet-->sucrose increases plasma cholesterol, triglycerides, uric acid and platelet aggregation
--lactose may be a risk factor in pre-menopausal women
--dairy and other animal proteins are more atherogenic than vegetable proteins (xanthine oxidase in homogenized milk mb causal, dairy products lower blood magnesium levels !!!)

DIETARY TREATMENTS
--increase intake of GLA and EPA, which are precursors to PGE1 and PGE3, inhibit platelet aggregation
--red wine has polyphenols which downregulate endothelin
--niacin -- in the form inositol hexaniacinate 1500 mg/day does not cause flush and does lower total cholesterol and triglycerides
--chromium-->decreased TG's and chol with increased HDL
--zinc-->drive down copper and lower HDL in males
--copper deficiency is atherogenic in animals
--vitamin E-->keeps glutathione peroxidase stocked-->keeps lipid peroxidase down
--vitamin C -->if chronically low this will increase cholesterol
--selenium --> if low more risk of heart dz
--magnesium --> when deficient promotes cardiac muscle contraction and increased clotting and insulin resistance, lowers HDL, increases platelet agg and lowers clotting time, excessive vitamin D and high dairy intake may intensify magnesium deficiency !!!

HOMOCYSTEINE
--derived from methionine during protein breakdown, then converted to harmless cystine by B6
--may have a toxic effect on EC's, impairs release of NO (can't vasodilate properly)
--may stimulate SMC proliferation
--thrombogenic = affects thrombomodulin and activation of protein C
--homocystinuria: hyper can be hereditary
--correlation to coronary artery dz (CAD) and peripheral vascular dz (PVD)
--lowered by folate and B6
--increased levels assoc w/ decreased B6, B12, and folate

ANEURISMS
--ETIO: atherosclerosis, cystic medial degeneration (familial), syphillis (tertiary), vasculitis (periarteritis nodosa, Kawasaki syndrome), trauma (AV fistulas), congenital defects (berry aneurism)
--most in aorta
--true = inside vessel wall
--false = pseudoaneurysm or pulsating hematoma is an extravascular hematoma that communicates with the intravascular space
--arterial dissection = blood enters wall and separates layers
--forms: saccular, berry, fusiform
--usual location for lesions: abdominal aorta between iliac bifurcation and renal arteries
--most in men over 50, familial, HTN, Marfan's
--sometimes in pregnancy (rare)
--atheromatous ulcers covered by mural thrombi, thinning and destruction of th emedia
--complications: compression of ureter or spinal erosion, adjacent vessel occlusion, abdominal mass, hermorrhage
--most common congenital: berry aneurism
--mycotic aneurysm dt infx of major artery, ex: septic emboli from IE or extension from local infx or direct invasion by bacteria
--mb iatrogenic: arterial cannulation, bypass surgery

ANGIITIDES
--= BV inflam
--arteritis, angiitis, and vasculitis are SYNONYMS
--often with necrosis
--presents with systemic and local sx
--"systemic necrotizing vasculitis"
--ETIO: immune, infx, trauma

POLYARTERITIS NODOSA = PAN
--usu young adult (any age)
--mb acute, subacute or chronic
--idiopathic necrotizing inflam of small/med muscular arteries (renal, coronary, hepatic, mesenteric)
--spares pulmonary vessels
--involves sharply localized segements usu at bifurcations
--intravascular thrombosis is frequent
--weakening can lead to aneurysms which can be felt as nodules
--marker for vasculitis: ANCA vs leukocytes, anti-neutrophil cytoplasmic Ab's
--course: S/Sx varied and puzzling due to many possible arteries to be affected, acute or chornic with remission periods
--organs most affected: kidney, heart, skeletal mm, skin, mesentery
--common S/Sx: FUO (fever of unknown origin), weight loss, rapid onset of HTN, abodominal pain and melena, muscular aches and peripheral neuritis
--more S/Sx: hematuria, albuminuria, HTN, abdom pain, melena, diffuse myalgia, peripheral neuralgia, fever, malaise, wt loss, star-like bruising pattern, arthritis, gangrene of fingers/toes, ulcers, livedo
--P-ANCA = perinuclear antineutrophil cytoplasmic antibodies often present in serum and refelct dz activity
--Dx: P-ANCA, arterial biopsy of kidney or nodular skin lesions, and angiography.
--PROG: fatal if not treated, 90% remission or cure with steroids and cyclophosphamide (destroys proliferating lymphoid cells)
--morphology: pathcy (under 1mmin length), fibrinoid necrosis* surrounded by acute inflam response in adventitia, thrombosis in lumen may-->infarct, may form aneurysm
--*fibrinoid necrosis = a strutureless eosinophilic mass that stains for fibrin
--ETIO: idiopathic, mb assoc w/ HBV antigen

TEMPORAL ARTERITIS = GIANT CELL ARTERITIS
--most common vasculitis
--mostly older folks, average age 70
--affects small and med sized arteries esp cranial vessels (temporal, vertegbral, opthalmic)
--ETIO: HLA-DR1 antigen, mb rxn vs elastin
--MORPH: granulomatous lesions w/ giant cells (2/3), lymphocyte and eosinophil infiltration of artery wall, intimal fibrosis, thrombosis possible, healed stage w/ scarring may feel fibrous
--more in nordic races
--course: onset insidious or sudden with headache, tenderness or pain and erythema over affected artery, visual loss (40%) and facial pain, usuall benign and self-limiting (6-12 mo)
--S/Sx: h/a,throbbing temporal pain, skin tenderness and erythema over vessel, 50% have visual effects, possible blindness, affected artery is cord-like, flu-like, myalgia, fever, arthral GIA
--a systemic illness associated with 50% of cases is POLYMYALGIA RHEUMATICA
--Dx: typical presentation, biopsy in 1/3 of cases, hiGh ESR, 2/3 of cases with giant cell or other focal changes
--TX: corticosteroids
--ETIO: idiopathic
--MORPH: granuloma of media and intima, giant cells at internal elastic lamina (IEL), simple: swollen, irreg, fragmented IEL, advanced: IEL disappears, intima thickened, media fibrotic, thrombosis may obliterate lumen.

KAWASAKI SYNDROME
--mucocutaneous lymph node syndrome
--ETIO: idiopathic
--MORPH: like an infant form of PAN with less fibrinoid necrosis and with a predeilection of the coronary vessels. full thickness of coronary arteries may be necrotized, or ther emay be only mild changes of the intima. vessels mb weakened with thrombosis, aneurysm, and rarely rupture.
--S/Sx: fever 102 ish mb intermittent, colicky abdominal pain, trunk and perineal rash (erythematous, macular, or pruritic), a few days later red redy fissured lips, pharyngitis (injected), conjunctival injection and strawberry tongue. Pallor of proximal nailbeds.
--S/sx: fever, LAD, rash, usu self-limiting but mb fatal, 20% w/ coronary arteritis-->aneurysm, a cause of MI in kids
--S/Sx: in 3-5th day of illness, erythema or purple/red discoloration of palms and soles with dedema (tense, non-pitting). Periungal, palmar, and plantar descquamation may follow about 10 days into rash. Cardia sx in 5-20% of pts begins on 10th day and may cause myocarditis, CHF, pericarditis, tamponade, arrhythmias, thrombosis,infarction or coronary artery aneurysms
--may last 2-12 weeks or longer
--Dx: typical presentation, anti-endothelial ab's, immune complexes
--LABS: leukocytosis, thrombocytosis, elevated ESR
--Tx: (allopathic) ASA and gamma globulin
--Incidence: epidemic in Japan, rare but increasing in US
--worst in coronary aa, leads to heart dz
--MORPH: like PAN
--children up to 5 years of age

THROMBOANGIITIS OBLITERANS = BUERGER'S DISEASE
--segmental, thrombosing, acute and chornic inflam of intermediate and small arteries (veiwns with phlebitis) of the extremities
--ETIO: almost exclusively in men aged 20-40, (5% women) who are HEAVY SMOKERS.
--MB vasoconstriction, thrombosis, EC toxicity, hypersensitivity to components of cigs
--course: nodular phlebitis, Raynaud's, instep claudication (less w/ exercise). Later-->excruciating pain, gangrene.
--Tx: smoking cessation allows remission

RAYNAUD'S DZ
--paroxysmal pallor or cyanosis of digits of hands or feet dt intense vasospasme
--no microscopic morphologic changes
--raynaud's "phenomenon" is dt arterial narrowing secondary to SLE< PSS, AS, Buerger's Dz
--PSS = progressive systemic sclerosis
--onset usu in teen years
--triggered by cold, emotions

VENOUS CONDITIONS
--thrombophlebitis = phlebothrombosis
----venous thrombosis leads to inflam of the vein
--site is deep leg vains in 90% of cases, also periprostatis in men and pelvic in female
--in the absence of leg trauma neoplasia must be ruled out
--Predisposing factors: immobilization, prlonged bed rest, pregnancy, obesity, post-operative states, standing a lot
--PHLEGMASIA ALBA DOLENS aka "milk leg" in pregnant females or immediately postpartem
--MIGRATORY THROMBOPHLEBITIS usu in pts w/ neoplasms (esp pancreas, lung, colon)
--S/Sx: swelling of leg, pain, pulmonary embolism may be first sign, Homan's sign (foot flex & compress gastroc)
--Dx: Doppler exam

VARICOSITIES
-dilated tortuous veins dt prlonged increased intraluminal pressure
--types: varicose veins, hemorrhoids, labial varicosities, esophageal varices (liver dz), variococele (papiniform plexus)
--ETIO: family tendency
--long periods of standing, driving or air travel
--MORPH: dilation of venous wall with valve deformities (thickening, rolling, shortened cusps)
--valves become incompetent
--thinning and hypertrophy
--mb spotty calcifications in media (phlebosclerosis)
--S/Sx: on lower extremity, skin may develop stasis dermatitis = mottled hyperpigmentation in lighter skin types and mb edema and ulceration