Vascular Flashcards
atherosclerosis
disease of arterial intimal thickening due to lipid accumulation, chronic inflammation, and repair
muscular and elastic arteries
contains: calcification, cholesterol clefts, necrotic core, fibrous cap
modifiable risk factors for athersclerosis
multiplicative
- smoking
- HTN
- obesity
- DM
- dyslipidemia
also: inflammation (high CRP) and physical inactivity
atherosclerosis pathogenesis
injured endothelial cells and dysfunction-> increase permeability and leukocyte and platetlet adhesion-> accumulation of lipid in tunica intima-> monocyte recruitment-> foam cell-> recruit sm. muscle cells and T cells-> Sm. muscle cell proliferation and ECM deposition
How does hyperlipidemia contribute to atherogenesis?
high levels of cholesterol increases local reactive oxygen species causing membrane and mitochondrial damage and accelerate NO decay
foam cells formation
macrophages (sm. muscles too) take up modified LDL through scavenger receptors that lack feedback inhibition and are unable to degrade them
release GF, cytokines, chemokines
What is the role of inflammation in atherosclerosis?
cholesterol crystal and FFA activate inflammasome leading to activation of IL-1: recruits leukocytes
inflammatory cells breakdown ECM and result in unstable plaques
IL-1 and TNF-a: decrease superoxide dismutase, NO, PG
factors implicated in sm. muscle proliferation in atherosclerosis
PDGF, FGF, TGF-alpha
stabilizes plaques
neovascularization of later atherosclerosis
O2 can’t get through thickened artery
hemorrhage into plaque making it prone to rupture
internal elastic lamina
separates tunica intima and tunica media
arteriovenous fistula
direct connection between arteries and veins bypassing capillaries
fibromuscular dysplasia
focal irregular arterial wall thickening with intimal and medial hyperplasia and fibrosis leading to luminal stenosis
renal, carotid, splanchnic or vertebral arteries in young women
hyperplastic arterioloscerosis
concentric wall thickening due to smooth muscle hyperplasia and hypertrophy
onion skinning
cause: malignant HTN, scleroderma can cause similar look of large interlobar renal arteries, lupus
fibrinoid change/necrosis
leakage of plasma protein into wall with or without necrosis
cause: malignant HTN or vasculitis (esp. polyarteritis nodosa)
hyaline arteriolosclerosis
wall thickening due to leakage of plasma protein into wall and increased secretion of matrix by smooth muscle cells
cause: HTN, DM
differential should include amyloidosis (larger vessels) and fibrinoid change
medial calcific sclerosis
Monckeberg
degenerative calcification of internal elastic lamina spreading into tunica media
canakinumab
trial drug
anti-interleukin-1B Ab
Tx:unstable plaque in acute coronary syndrome
What makes a plaque unstable?
thin fibrous plaque: prone to rupture and release thrombogenic material form necrotic
colchicine
gout drug that can be used at low doses in athersclreosis
angiogram
shows lumen of vessels only
intravascular ultrasound
shows wall and lumen of vessels
mechanism of acute coronary syndrome
rupture of atherosclerotic plaque due to erosion of fibrous cap (usually thin) and release of thrombogenic material
ruptured plaques: large lipid core, thin cap, abundant inflammatory cells, calcification
erosion of atherosclerotic plaque
- oxidative stress and hypochlorous acid cause endothelial cell apoptosis producing TF
- modified LDL can induce MMP-14 -> MMP-2-> degradation of type IV collagen
- Lp-PLA2-> MCP-1, ICAM-1, VCAM-1 -> endothelial cells vasodilator less in response to NO and undergo apoptosis
- Lp-PLA2-> MCP-1 on macrophages-> IL-1beta
What causes atthersclerotic events?
up to 75% rupture
up to 25% erosion
most events are due to superimposed thrombosis
How do statins and aspirin prevent atherosclerotic event?
statins: reduce lipid content, making more fibrous, decrease macrophages
may be anti-thromboic, pro-fibrinolytic, vasodilatory
aspirin: anti-platelet
What is the role of T cells in atherosclerotic plaques?
- secrete IFN-gamma that inhibits sm. muscle cells from making collagen required for fibrous cap
- boosts macrophage collagenases through its CD40 ligand
What is the role of macrophages in atherosclerotic plaques?
overproduces MMP-1, MMp-8, MMP-13 that degrade collagen
distribution of atherosclerosis
- lower abdominal aorta
- coronary arteries
- popliteal arteries
- internal carotid arteries
Which coronary arteries are most likely to have acute coronary disease?
- LAD (1/2)
- RCA (1/3)
- LCX (1/6)
atherosclerotic stenosis
early stages: remodeling of artery expands it outward and preserves lumen, eventually impinges on lumen
critical stenosis
occlusion that produces tissue ischemia, 70% reduction of lumen cross section
Sx develop: angina on exertion
effects of occlusion depend on metabolic demand and arterial supply of tissue
general categories of acute plaque changes
- rupture: releases thrombogenic plaque constituents into blood
- erosion: exposes subendothelial basement membrane to blood
- hemorrhage into atheroma: expanding its volume
When are MI most likely?
6am-12pm
due to adrenergic stimulation associated with waking and rising
also intense emotional distress
methotrexate use in atherosclerosis
inhibition of proliferation fibroblasts, sm. muscle cells, endothelial cells, lymphocytes that play a role in atherosclerosis
thrombosis of coronary arteries in the young
- vasospasm (cocaine, amphetamines)
- lupus anticoagulant in young woman
hypercoaguable states lead to VENOUS thrombosis
atheroembolism
most likely in leg, renal, intestinal arteries from aorta
RARE in coronary arteries
dissection
tear of tunica intimal letting luminal blood under high pressure into the tunica media making a second lumen
ectasia
non-discrete, non-localized dilatation of blood vessel or duct
fibrillin
extracellular glycoproteins essential for structuring elastin fibers
Marfan syndrome
autosomal dominant
inherited disease of defective fibrillin (FBNI gene) and excess TGF-beta leading to tall thin body habits and cystic medionecrosis of ascending aortic (dissections)
Tx: beta-blockers
Ehlers-Danlos
usually autosomal dominant
heterogeneous group of inherited disorders due to defects in synthesis or structure of fibrillar collagen
COL3A1 gene for type III collagen
spontaneous rupture of blood vessels and intestines
aortic aneurysm
elderly, fam. Hx, white males
combination of atherosclerosis and predetermined degeneration of tunica media (increased MMP)
other causes: Marfan, infection, vasculitis
abdominal more common
Sx: usually none; back pain if leaking
Dx: imaging
Tx: stent, surgery (not until 5 cm)
complications: RUPTURE, thrombus, embolism, obstruction, aortoenteric fistula
aortic dissection
late, middle age, men blacks
rarely obvious what causes it, medial dissection associated with cystic medial degeneration
Sx: tearing chest pain or between scapulae that moves as dissection progresses, with or without altered mental status (carotid), arm pain/weakness (subclavian), collapse (rupture into pericardium or left pleural cavity)
DX: CT, MRI, transesophageal echo
Tx: reduce BP, surgery
giant cell arteritis
temporal arteritis
elderly, white, female, N. European Hx
Sx: headache, visual distrubance, jaw claudication, scalp tenderness
complication: blindness
inflammation: segmental, transmural, granulomatous, giant cells on internal elastic
membrane
innate and adaptive
PAMP-> dendritic cells (TLR-4) produce IL-12 and IL-18 (also IL-2, IL-6) -> up regulate Th1 cell production of IFN-gamma, Th17 (IL-1, IL-23) and release homing CCL19 and CCL21-> bind CCR7 receptor-> arrest of dendritic cells -> trapped in arterial wall
IFN-gamma-> VEGF and PDGF -> fibrosis and stenosis
MMP-2 and MMP-9: destroy elastin
Tx: anti-TNF and corticosteroids: suppress IL-1, IL-6, IL-17 (Th17)
Takayasu arteritis
young East Asian females
cpture, hemopericardium (cardiac tamponade)
Sx: pulseless arm, arm claudication, subclavian or aortic bruit, aortic or major branches stenosis, angina
inflammation: segmental, transmural, necrotizing, loose granulomas (multinucleate giant cells)
complications: aortic dissection, rupture, hemopericardium (cardiac tamponade)
Tx: corticosteroids
poor prognosis
polyarteritis nodosa
white, male, 40s
Sx: neuropathy (wrist or foot drop), renal failure, ACUTE ABDOMEN, cholecystitis, pancreatitis, angina pectoris, livedo reticularis
inflammation: segmental, transmural, nodular, FIBRINOID necrosis
SPARES LUNGS, lesions at DIFFERENT PHASES
complications: thrombosis, occlusion, rupture, aneurysm
NO Ab
prognosis: good with treatment
Kawasaki disease
East Asian children
Sx: conjunctival injection, desquamtion rash, cervical lymphadenopathy, strawberry tongue, hand and foot erythema/ edema, fever
complications: coronary aneurysm, thrombosis, MI, sudden death
Tx: aspirin and IV immunoglobulin
microscopic polyangiitis
hypersensitivity or leukocytoclastic vasculitis
all lesions SAME PHASE
necrotizing glomerulonephritis and pulmonary capillarities common
Ab: P-ANCA (MPO)
segmental, fibrinoid necrosis
Sx: hemoptysis, hematuria, proteinuria, bowel pain, bleeding, muscle pain/weakness, palpable purpura
Tx: corticosteroids, immunosuppression
granulomatosis with polyangiitis
Wegner’s, white, 40’s
necrotizing granulomatous: arteries and veins in upper and lower respiratory tract and kidneys
GEOGRAPHIC with histiocytes
Ab: C-ANCA (proteinase-3)
Tx: corticosteroids, immunosuppression, rituximab
Churg-Strauss syndrome
allergic granulomatosis with polyangitis
asthma, eosinophilia, vasculitis
Buerger disease
young, male, smoker, Middle Eastern or South Asian
thrombosing faso-occlusive disease of arteries and veins of limbs
ischemic ulcers. gangrene moving distal to proximal
granulomas and giant cells
Tx: stop smoking and amputation
peripheral arterial disease
common, elderly, men
chronic atherosclerotic occlusive disease of large and medium arteries, primarily legs
Sx: intermittent claudication (during exercise), pain at rest is severe
signs: lost pulses, bruits, pallor, skin/muscle atrophy, ulceration, necrosis
Dx: Hx and physical
Tx: exercise
acute arterial occlusion
uncommon
thromboemboli mostly from heart
Sx: pain, pallor, paralysis, paresthesia, pulselessness in legs (arms and brain too)
Dx: Hx and physical
Tx: anticoagulation, thrombolytics, surgery, thromboectomy
SURGICAL EMERGNCY
large vessel vasculitis
- Temporal (giant cell) arteritis
- Takayasu arteritis
PULSELESS
medium vessel vasculitis
- polyarteritis nodosa
- Kawasaki
- Buerger
INFARCTION
small vessel vasculitis
- granulomatosis with polyangitis (Wegner’s)
- microscopic polyangitis
- eosinophilic granulomatosis with polyangitis (Churg-Strauss)
- Henoch-Sconlein purpura
PALPABLE PURPURA
aneurysm
discrete localized dilatation of blood vessel (or heart)
cysitc medial degeneration
loss of sm. muscle cells and plastic fibers in tunica media of large arteries
leads to: aneurysm
Type A aortic dissection
ascending aorta with/without other parts of aorta
must have rapid Dx
Tx: anti hypertensives, surgery
Type B aortic dissection
descending aorta alone
Tx: anti-hypertensives
vasculitis
inflammation of blood vessels
most autoimmune
most common Sx: fever, myalgia, arthralgia, malaise
Dx: biopsy
palpable purpura
erythematous tender skin nodules
infectious vasculitis
caused by : 1. fungal (Aspergillus) 2. bacterial (pseudomonas) 3. viral (CMV) may cause mycotic aneurysm (even if not fungal)
