2 MECHANISM OF VASCULAR DSE.

narrowing or complete obstruction

weakening

T. intitma endothelial cells with relaxing factors (NO) and contracting

T. media smooth muscle & ECM factors (endothelin)
T. adventitia loose CT, nerves, BV w/ interendothelial junctions opens under
hemodynamic stress (BP) or vasoactive agents
VASCULAR (histamine during inflammation)
1.LARGE ARTERIES different functions or behaviors in various
aorta, arch vessels, iliac & pulmonary a places:
T. media with elastic fibers alternate w/ smooth hepatocytes or renal glomeruli w/
muscle cells fenestrations to facilitate filtration
w/ age stiff pipes BP OR dilated & tortous CNS BBB
rupture to maintain normal, non-thrombogenic
2. MEDIUM SIZED MUSCULAR endothelial lining:
Coronary & renal a laminar flow
T. media made 1 w/ smooth m. cells VEGF
w/ elastin at internal & external elastic lamina normotension / firm adherence to lining
3. SMALL ARTERIES (<2 mm) ; ARTERIOLES (20-100um)
T. media made 1 w/ smooth m. cells
Regulates blood flow/ resistance when
pressure drops blood flow becomes steady
(instead of pulsatile)
4. CAPILLARIES
7-8 um (like RBC)
Lined by endothelial cells, surrounded by
pericytes
Large cross sectional area and slow flow ideal
for exchange of nutrients / substances
Metabolically active organs has highest capillary
density (ex. )
5. VEINS endothelial activation / activated state induced
larger diam. / lumina & thinner walls more by ( see diagram)
prone to dilatation, ext. compression & Some responses are rapid & reversible others
penetration by tumors may take days to develop & abate and may
Valves prevent backflow in areas that flow involve alteration in gene expression & protein
against gravity (ex. Legs) synthesis. Exposure in high amounts for a
highest volume (2/3) prolonged period may lead to endothelial
6. LYMPHATICS dysfunction leading to vasodilation,
drains fluid from the tissues & returns it to the hypercoagulable state, O2 free radical
blood via thoracic duct production promote atherosclerosis
contains mononuclear inflammatory cells & vascular lesion of HPN & diabetes
protein VASCULAR SMOOTH MUSCLE CELL
can disseminate dse or infection & tumors to Participates in repair & pathologic process
distant site (metastasis) Pro-growth factors:
ENDOTHELIUM PDGF
lines blood vessels endothelin
maintains: non-thrombogenic state thrombin
modulate inflammation affect growth of Fibroblast GF
other cell types IFN-
IL-1
Factors that maintain quiescent state:
NO
Heparan SO4
TGF
CONGENITAL VASCULAR
BERRY ANEURYSM
 - thin walled arterial outpouchings in cerebral vessels Types:
- common around circle of willis A. ESSENTIAL (95%)
- can result in intracerebral hge Idiopathic
AV FISTULA Multifactorial :
- abnormal connections between arteries & veins 1. Na excretion
- occur either as developmental defect OR rupture of 2. Vascular resistance from chronic
arterial aneurysm into adjacent vein (inflammatory necrosis vasoconstriction
or penetrating injuries) 3. Genetic polymorphism
- created to use as access for hemodialysis 4. Environmental : obesity, smoking, stress,
- extensive AV fistulas high output cardiac failure sedentary lifestyle, salt intake
FIBROMUSCULAR DYSPLASIA B. SECONDARY
- irregular thickening the walls of medium & large arteries 2 to an underlying condition: Renal
due hyperplasia & fibrosis of t. media & t. intima Endocrine / adrenal Cardiovascular
- luminal stenosis Neurologic
vessel spasm that reduce blood flow Risk factor for development of : atherosclerosis
renovascular HPN (in kidneys) CHF RF
BLOOD PRESSURE Morphologic pathology:
HYALINE HYPERPLASTIC
Systemic BP must be maintained to prevent: arteriosclerosis arteriosclerosis
HYPOTENSION can lead to inadequate perfusion, organ
Benign HPN Severe HPN
dysfunction and tissue death
Thickened wall with Onion skin, concentric,
HYPERTENSION can lead to vessel & end organ damage
- risk factor for atherosclerosis deposition of amorphous laminated thickening
proteinaceous material
(hyalinized)
Luminal narrowing Luminal almost lost
In kidneys glomerular Accompanied by fibrinoid
scarring or deposits & vessel wall
nephrosclerosis necrosis (necrotizing
arteriolitis)
Also seen in elderly
Renin- released (normotensive) ; diabetic
by JG cells due
microangipathy
to: BP
cathechol.
BLOOD PRESSURE = CO x PERIPHERAL RESISTANCE
CARDIAC OUTPUT
= STROKE VOLUME x HEART RATE
myocardial contractility
(adrenergic system)
Filling pressure regulated through Na hemostasis
PERIPHERAL RESISTANCE
balance between vasoCONSTRICTORS &
vasoDILATORS
Fine tuned by blood ph and hypoxia

RENIN- ANGIOTENSISN SYSTEM

- way by which kidneys influence periph. resistance & Na
excretion / retention

INTIMAL THICKENING
Response to vascular injury
Triggered by cellular loss or vessel dysfucntion
Formn of neointimal cells that have migratory,
proliferative & synthetic properties
irreversible may eventually cause stenosis of
AII - BP thru: vessel
vascular smooth m. part of normal aging
contraction Na
tubular resorption
stimulating ARTERIOSCLEROSIS
hardening of arteries
thickening & loss of elasticity
NO & PG counter balances angiotensin vasopressor 3 types:
effect 1) Arteriosclerosis
- relaxes vascular smooth m. Small arteries & arterioles
Hyaline & hyperplastic
HYPERTENSION 2) Medial calcification
 Calcific deposits in medium arteries: radial &
uterine a. (Monckeberg sclerosis)
>50 y/o
3) Atherosclerosis

ATHEROSCLEROSIS
presence of intimal lesion atheroma (atheromatous or
atherosclerotic plaques)
raised lesions w/ soft grumous lipid core
(cholesterol, chol.esters, necrotic debris) & fibrous cap
(vulnerable plaque)
obstruct vascular lumina prone to rupture
thrombosis
Risk factors:
Non Modifiabl Others
modifiabl e
e/
Constitut 2 most common causes of Endothelial injury are :
ional 1) Hemodynamic disturbance - common in vessels at
Genetics Hyperlipid Inflamn ostia of exiting vessels
emia branch points turbulent flow
Hypertens CRP post wall of abdominal aorta
ion 2) Hypercholesterolemia
age Obesity Homocysteine Morphology
Family Hx Inflammat Lipoproteins (Apo B- 1) Fatty Streak
ion 100, A) - minute, yellow FLAT lesions
DM Metabolic syndrome - 1cm or more in length
(obesity - w/ lipid filled foamy macrophages
Procoagulants 2) Atherosclerotic plaque
- white-yellow RAISED lesions
thrombin
- 0.3-1.5 in diam
Type A personality
- Patchy
- Periphery shows neovascularization
20% occur in the absence of any risk factor SITES OF ATHEROSCLEROSIS: Abdominal aorta ,
Genetics: familial hypercholesterolemia Coronary, Popliteal & ICA
Women protected until menopause Cxs: Aneurysm
Age: 4x in 40-60 y/o Thrombosis
DM : assoc w/ hyperlipidemia & HTN HTN
abnormalities of coagulation, platelet adhesion / Cerebral Atrophy
aggreg, inc. oxidative stress, fxnal change in Peripheral A. Dse
endothelium - Claudication (angina pain when
Hyperchol: LDL HDL walking, relived at rest)
LDL transport cholesterol to peripheral tissues
HDL transport cholesterol to liver for detox - other sxs: dependent rubor
Cool skin temp
Beneficial Not Beneficial Poor wound healing
Exercise High intake of decreased growth of hair &
Cholesterol & nails
diminished pedal pulse
Saturated fat (yolk,
bruits over femoral or
butter, animal fat)
popliteal a.
-3 Fatty acid Trans fat - 5 Ps in acute vessel occlusion: Pain,
(abundant in (Unsaturated) seen Pallor, Paresthesia
Fish oil ) in margarine
Statins (inhibit Paralysis, Pulseless
HMG CoA - DX: Ankle branchial Index (ABI),
reductase) angiography & UTZ
- TX: Manage RF, Revascularization &
CRP predicts the risk of MI, stroke, peripheral a. dse Cilostazol (Plt agg inhib)
& sudden cardiac death; marker for disrupted
inflammatory plaques ATHERESCLEROTIC PLAQUE
Homocysteine can detect early onset vascular dse CLINICAL CLINICAL
Pathogenesis due to intimal thickening in response CHANGES CONSEQUENCES
to cellular injury thrombus formn = response to Rupture, MI, attack
injury hypothesis ulceration,
erosion
Hge Stroke, Cerebral
infarction
Embolism Gangrene,
Aneurysm, PVD
Aneurysm
 MC in men, smokers, <50 y/o
Caused by atherosclerosis
MC site : in between renal a. & aortic bifurcation (below
renal a. orifice)
Usually accompanied by smaller iliac a. aneurysm
MYCOTIC AAA salmonella gastroenteritis seed the
aneurysmal wall or thrombus
INFLAMMATORY AAA dense periarortic fibrosis w/
inflammatory cells
PATHO: Vessel wall weakens, lumen fills w/ atheromatous
debris & clots
Absence of vasa vasorum
Structural defect in CT
TRIAD: Pulsatile mass, Left flank pain, Abdominal mass
Critical Stenosis tipping point of arterial occlusion at which CONSEQUENCES
demand exceeds supply 1. Obstruction of vessel branching off the abd. Aorta
At rest, px have adequate perfusion but with modest (iliac, renal, vertebral, mesenteric) distal ischemia
exertion demand exceeds supply stable angina (chest 2. Embolism
pain develops bec. of cardiac ischemia) 3. Impingement of adjacent structure (ureter or
vertebrae)
Chronic arterial hypoperfusion bowel ischemia 4. Abdominal mass
sudden cardiac death 5. Rupture (<4cm diam DOESNT rupture)
chronic IHD Risk for IHD & stroke
ischemic
encephalopathy THORACIC AORTIC ANEURYSM
intermittent Assoc. w/ HPN & Marfan Syndrome (mutation on TGF-)
claudication CONSEQUENCES:
Plaque erosion or rupture thrombosis vascular 1. Compression of mediastinal structure (DOB or
obstruction swallowing)
tissue 2. Persistent cough from irritation of recurrent laryngeal
infarction n.
3. Pain due to erosion of bone
Vulnerable plaque (cap) 4. dse due to valvular insufficiency or narrowing of
- pathognomonic lesion ostia
5. Aortic rupture
- thin fibrous cap
- SMC, foam cells, inflammatory POPLITEAL ARTERY ANEURYSM
cells & extracell. lipid MC peripheral a. aneurysm
- w/ necrotic center (CH crystals, Pulsatile mass behind knee
cellular debris & foam cells
ANEURSYM
BERRY ANEURYSM
Congenital or acquired dilations of BV or Cerebral a. in circle of willis at base of brain
TRUE : involves all 3 layers of BV or the attenuated wall MC site: jxn of communicating branches of ACA (ant
of the cerebral a)
FALSE : aka pseudoaneurysm; wall defect leads to RF: Atheresclerosis, HTN, COA, Stress
formation of a hematoma that communicates with the PATHO: lacks internal elastic lamina & smooth muscle
intravascular space CP: sudden onset of severe occipital HA worst
SACCULAR : discrete, 5-20 cm in diam, often w/ a headache I ever had
thrombus inside (Berry Aneurysm) Nuchal rigidity
FUSIFORM : circumferential up to 20 cm diam; involves
abdominal aorta (MC) , aortic arch, iliac a. SYPHILITIC ANEURYSM
Occurs when structure or function of the connective Cx of 3 syphilis (t. pallidum)
tissue is compromised thru: PATHO: Spirochete infects vasa vasorum of ascending &
inadequate or abnormal CT synthesis transverse portion of aortic arch Vasculitis
xssive CT degradation (endartritis obliterans) plasma c. infiltrate intense
loss of smooth muscle inflamn occludes lumen of vessel vessel ischemia
Causes : atherosclerosis HPN trauma vasculitis AV regurgitation & dilatation of aorta & AV ring
congenital defect infection (Mycotic aneurysm) CP: AV regurgitation (diastolic murmur) leads to
Fungi: Aspergillus, Candida, Mucor wide pulse pressure (bounding pulse) & Austin Flint
Bacteria: B. fragilis, P. aeri, murmur (diastolic)
Salmonella brassy cough (irritation of Left recurrent laryngeal
n)
DISSECTION
Pressurized blood gains entry into an arterial through a AORTIC
surface defect and pushes apart underlying layers Occurs when blood splays apart the laminar planes of

Aneurysm & dissection impt causes of stasis & the media to form a blood-filled channel within the aortic
thrombosis w/ propensity to rupture wall
Risk factors:
ABDOMINAL AORTIC ANEURYSM 1. Men, 40-60 y/o w/ antecedent HPN
 2. Young w/ CT abnormalities (Marfan, Ehler danlos, REYNAUDS PHENOMENON
defect in Cu metabolism) - red white-blue from proximal distal
3. Iatrogenic (S/P arterial bypass sx OR arterial Proximal dilation, central vasoconstric, distal cyanosis
cannulation during dxtic catheterization) 1 / Reynauds Disease
4. Pregnant in response to cold or emotion
Types: affects 3-5% of population
Proximal / Type A : no structural change xcept late in course of dse
DeBakey I ascending & gangrene is rare
descending aorta 2 - due to other entity: Buerger dse, SLE, scleroderma
DeBakey II ascending
only MYOCARDIAL VASOSPASM
Distal / Type B : xssive constriction of arteries or arterioles ischemia
DeBakey III beyond infarction
Subclavian A. pptd by vasoactive mediators: Endogenous
(Epinephrine from Pheochromocytoma)
Exogenous (Cocaine,
Phenylephrine)
Thyroid hormone
Xtreme psychological stress & release of
catecholamine
AutoAbs & T cells in Scleroderma
Cardiac Reynaud occurs when vasospasm last > 20
mins
CP: Sudden onset of excruciating or stabbing pain in Takotsubo cardiomyopathy / broken heart syndrome
chest then radiates to back between scapula then Ischemic dilated cardiomyopathy due to
downwards as dissection progresses exacerbated ischemia
Cardiac sx: MI, aortic insufficiency, tamponade PATHO FINDING: Contraction band necrosis myocyte
Other sxs related to extension of dissection into great hypercontraction
arteries of neck, renal, mesenteric & iliac obstruction
Compression of Subclavian A. loss of pulse in upper
ext VEINS &
Cause of death: rupture into peritoneal, pericardial or
pleural cavity VARICOSE VEINS
Management: Type A rapid diagnosis, anti-HPNsive & Abnormally distended (>3cm) & tortous veins
plication of tear LOCATIONS:
Type B conservative 1. Superficial saphenous veins (legs)
2. Distal Esophagus (esophageal varices from portal
VASCULITIS HPN)
Inflammation of vessel wall 3. Anorectal (hemorrhoids)
Etio: Non-infectious (Immune mediated) Infectious 4. Scrotal sac (varicocele)
5. Periumbilical veins of abdominal wall (caput
NON-INFECTIOUS VASCULITIS medusae)
1. Immnune complex deposition Incompetent valves stasis, congestion, edema, pain
Seen in SLE & thrombosis
Implicated in Drug HPS (penicillins) reversal of blood flow to
2 to Infxn superficial saphenous v.
2. Anti-neutrophilic Cytoplasmic Abs (ANCAs) Persistent edema stasis dermatitis & ulceration
Antiproteinase-3 (PR3-ANCA) Embolism rare
formerly c-ANCA
VENOUS THROMBOSIS
PR3 neutrophilic azurophilic granule CAUSES : stasis of blood flow (prolonged immobilize of
assoc. w/ Wegeners granulomatosis >3 days, post op)
Anti-myeloperoxidase (MPO-ANCA) hypercoagulability (ATIII, OCP, pancreatic
formerly p-ANCA CA, Protein C & S deficiency,
MPO lysosomal granule involved in O2 Favtor V def)
free radical gen SITEs : deep vein of lower ext
induced by several therapeutic agents periprostatic / ovarian
(Propylthiouracil) uterine
seen in Polyangitis & Churg strauss portal / hepatic
3. Anti-endothelial cell AB dural sinuses of brain
Seen in Kawasaki dse RISK FACTORS : CHF, pregnancy, OCPs, obesity
4. Auto reactive T cell
DEEP VEIN THROMBOSIS
INFECTIOUS VASCULITIS ACUTE SIGNS : Swelling of affected leg >3cm in diam
infectious agent: bacteria or fungi (Mucor, more than the other leg
Aspergillus) Homans sign (pain on dorsiflexion of foot &
direct invasion or hematogenous spread squeezing calf muscles)
may weaken vessel wall mycotic aneurysm Pitting edema distal to thrombosis
CHRONIC SIGNS : Stasis dermatitis (orange discoloration
DISORDERS OF BLOOD
around medial malleolus of the ankle)
inappropriate exaggerated vasoconstriction
 CX: Pulmonary embolism TX: Corticosteroids
Takaya Involves medium & large vessels
SUPERIOR VENA CAVA SYNDROME sus CP: Initially fatigue, weight loss & fever;
Compression of SVC by a 1 lung CA (95%) Arteriti ThenBP & pulse in Lower Ext; Distal aorta
{bronchogenic or small cell} or mediastinal lymphoma s/ leg claudication; Pulmonary a. Pulm HPN
Purple or bluish discoloration of face; respiratory distress Pulsele >50 y/o Giant cell aortitis
ss dse <50 y/o Takayasu aortitis
INFERIOR VENA CAVA SYNDROME transmural scarring & thickening
Compression of IVC by a neoplasm or thrombus from
TX: Corticosteroids
renal, hepatic or lower extrem. Vein
PAN Small & medium arteries Vessels: Kidney, ,
Lower extrem edema; distention of collateral v. of
abdomen liver, GI (SPARES pulmonary vessels)
CP: arms falls asleep at night, numbness & paresthesia, Young adults
Adson Test (pulse disappears when arms are CP: Presents w/ malaise,fever, weight loss
outstretched and px looks to arm) segmental fibrinoid necrosis w/ or w/o
thrombosis
THORACIC OUTLET SYNDROME Associated w/ Hepa B
Compression of neurovascular compartment of the neck TX: Corticosteroids
CAUSES: cervical rib, spastic scalene muscle
Kawas Large & medium a
ACUTE LYMPHANGITIS aki / Acute, febrile, self limited dse.
Acute inflamn caused by bacterial seeding in lymphatic Mucoc < 4 y/o
vessels utaneo Coronary A. (can cause aneurysm
Due to incompetent basement membrane us rupture thrombose
Painful red streaks lymph Dense transmural inflammatory infiltrate
S.pyogenes node CP: edema of hands & feet; erythema of
syndro palms, soles, mouth & conjunctiva; cracking of
LYMPHEDEMA
me lips, strawberry tongue, desquamative rash;
Collection of fluid in interstitial space
cervical LN enlargement
1 : Familial (Milroy dse) or congenital
TX: IV Ig, ASA
2 / Obstructive from : tumors, post radiation fibrosis,
filariasis, post inflame thrombosis or scarring
Microc Capillaries, small arterioles, venules
Chronic edema brawny induration or peau d orange
ospic Lesions are at the same stage of inflamn
Rupture chylous or milky effusion into abdomen,
thorax or pericardium polyan Involves MC lungs & kidney; others: skin,
gitis / mucus membrane, brain, heart, GIT
HPS or CP: Palpable purpura, GN (crescentic),
VASCULITIDES Leukoc hemoptysis, hematuria, abd. Pain, muscle
Inflammation of the small vessels (arterioles, venules, yclocla weakness
capillaries) stic >80% assoc. w/ MPO-ANCA (p-ANCA)
Medium (muscular a) Vasculi
Large (elastic a) tis
PATHO: Type II HPS (immune cplx) Wegen TRIAD: Granuloma (lung or upper resp tract),
Type III HPS (Ag-AB) ers Vasculitis (Medium & small vessel), GN
ANCA : c-ANCA Abs against protein 3 Granul (crescentic)
(Wegeners) omatos 95% assoc. w/ PR3-ANCA (c-ANCA)
p-ANCA Abs against is CP: Bilat. pneumonitis w/ nodules & cavitation;
myeloperoxidase of neut
chronic sinusitis; mucosal ulceration of
(microscopic polyangitis, Churg
nasopharynx (saddle nose deformity)
strauss)
Direct invasion TX: Corticosteroid, cyclophosphamide
CP: Churg- Small vessels involving skin, lung, heart
Small Inflamn, HPS, HSP, microscopic Straus vessels
vessel purpura polyangitis s CP: Allergic rhinitis, asthma, peripheral
Medium Thrombosis, PAN, Kawasaki Syndro eosinophilia
infarction, me / >70% assoc. w/ MPO-ANCA (p-ANCA)
aneurysm Allergi
Large Loss of pulse, stroke Takayasu, Giant c
Cell arteritis granul
omatos
is /
Giant Involves large & small vessels especially in Angiiti
Cell temporal area s
Arteriti > 50 y/o Throm Medium & small a (Tibial A. & Radial A.)
s CP: Presents w/ fever & facial pain; Diplopia bangiti Men, before 35 y/o, smokers
/Tempo blindness s Genetic predilection: Jews living in Israel,
ral IEM: granulomatous inflamn infiltration of obliter Japanese & Indians)
arteriti lymphocytes, macrophages & multinucleated ans / CP: Cold induced Reynauds Phenomenon;
s giant cells fragmentation Buerge instep claudication; ischemic ulcers or
rs Dse gangrene of foot/toes
TX: smoking cessation, IV prostaglandin;
vasodilators