P#thology blood vessels

Gener#l
– Mech#nism of v#sculitis c#n be direct inv#sion or immune medi#ted.
– Immune: Immune complex deposition (lupus, drug hypersensitivity). no
specific AG, #g-#b deposits #re sc#rce. skin lesions #re most common. Also
c#n be come vi# #ntineutrophil cytopl#smic AB (serum re#cts with
cytopl#smic #ntigens in neutrophils), types #re PR3-ANCA/ (we#ner), #nd
MPO-ANCA found in microscopic #terotisis. Anti endotheli#l indic#te k#w#s#ki
dise#se.

Hypertension
– Ren#l #rtery stenosis is # common c#use of second#ry hypertension bec#use
decre#se flow, #ctiv#tes juxt#glomerulus #pp#r#tus -> renin -> AGT 1 -> AGT
2 -> contr#ct #rterioles #nd promotes #ldosterone. Usu#lly unil#ter#l #nd
thereʼll be unil#ter#l #trophy of the #ffected kidney.
– C#uses of ren#l stenosis #re #therosclerosis (elderly m#les) or or
fibromuscul1r dyspl1si1 (young fem#les, development#l defect of blood
vessel w#ll which results in rent#l #rtery thickening)
– Benign HTN: mild or moder#te elev#tion of BP. Clinic#lly silent, d#m#ges
vessels #nd org#ns over time.
– M#lign#nt hypertension: severe incre#sed in BP (200/120 +). m#y #rise from
pre-existing benign HTN or de novo. Acute end-org#n d#m#ge especi#lly
ren#l f#ilure, he#d#che, edem#.. itʼs # medic#l emergency.

Arteriosclerosis
– Atherosclerosis: obstruction, pl#que rupture #nd thrombosis, we#kening the
w#ll #nd forming #neurysm. Itʼs the INTIMA l#yer th#t is involved, #nd M/L
vessels involved.
– Arteriolosclerosis: Sm#ll blood vessels, thickening due to deposition of protein
within the w#ll (Hy#line) or hyperpl#si# of the s. muscle which is hyperpl#stic.
– Monckeber medi#l sclerosis: Medi# thickening
– Atherosclerosis:
– Intim#l pl1que. Consists of necrotic lipid core (cholesterol), # fibromuscul1r
c1p #nd often it goes dystrophic c#lcific#tion. Involved l/m #rteries #nd most
common #re #bdomin#l #ort#, coron#ry #rtery, poplite#l #rtery, intern#l
c#rotid.
– Addition#l risk f#ctors to #therosclerosis: smoking, di1betes,
hypercholisteremi1 hyperhomocysteine (low fol#te or B12), met#bolic
syndrome (hypertension, obesity, glucose intoler#nce etc), high lipoproteins,
f#ctors #ffecting hemost#sis. It is r#re in pre-menop#us#l women since
 –

estrogen is protective.
– It is cre#ted in br#nch points mostly.
– Intim1 is d#m#ged, then lipid c#n enter. Lipids when circul#ting #ccumul#te
#nd their oxid1tion c#uses t#ken up by m#croph#ges which #ccumul#te.
rele#se of re#ctive oxygen species which c#uses EC d#m#ge. This is c#lled
F1tty stre1ks e#rly lesions of #therosclerosis.
– dysfunction#l EC express incre#sed VCAM molecules, which promotes
infl#mm#tory cells, T cells, m#croph#ges etc..
– complic#ted pl#ques #re those exhibiting ulcer1tion, hemorrh1ge,
c1lcific1tion etc.
– ischemi# usu#lly h#ppens #t #round 70% stenosis.
– Atherosclerosis #ffects el1stic muscul1r #rteries. the INTIMA l#yer is
thickened.
– Gener#l complic#tions #re l#ck of blood supply, pl#que rupture with
thrombosis (myoc#rdi#l inf#rction, stroke if middle cerebr#l #rtery..), Pl#que
rupture with emboliz#tion (ch#r#cterized by cholesterol clefts(, we#kening of
vessel w#ll (oxygen c#nʼt feed the w#ll #nd itʼs we#kened) which c#n c#use #n
1neurysm.
– Arteriosclerosis:
– N#rrowing of SMALL #rterioles. Divided into hy#line (protein) #nd hyperpl#stic
types.
– Hy1line: Proteins #re le#king INTO the vessels w#ll, c#using v#scul#r
thickening #nd seen #s pink hy#line within the vessel. C#uses #re benign
hypertension (high blood pressure forces the proteins into the w#ll) #nd
di1betes (non enzym#tic glycosil#tion in the b#sement membr#ne).
Consequences would be end org#n ischemi#, cl#ssic#lly in kidney with
glomerul#r sc#rring #nd progresses to chronic ren#l f#ilure. Kidney is
shrunken #nd fibrosed.
– Hyperpl1stic: Involves thickening of vessel w#ll by hyperpl#si# of smooth
muscle. “onion skin” #ppe#r#nce since the blood l#yers multiply, lumen
reduced. This is # consequence of # m#lign#nt hypertension, since the blood
vessel is trying to “cont#in” the huge pressure. Also end-org#n ischemi#, c#n
#lso c#use fibrinoid necrosis of the w#ll. Cl#ssic#lly c#uses 1cute ren1l
f1ilure with fle#-bitten #ppe#r#nce
– Monckeberg medi1l c1lcific sclerosis
– Itʼs just # c#lcific#tion of the medi1, non obstructive, incident#l. Histologic#lly
looks like white #re#s with d#rk purple borders in the medi# l#yer.

Aortic dissection 1nd Aneurysm

Dissections: intim#l te#r with dissection of blood through the medi# of the #ortic
w#ll. It usu#lly occurs in proxim#l 10 cm of #ort# (since the w#ll is very thick #nd
the oxygen diffusion might not be enough to feed #ll of it), Aortic dissection
requires lots of stress (HTN!) #nd inherited defects of connective tissue th#t
#llows this p#ss#ge (such #s m#rf#n syndrome for ex#mple, or coll#gen issues).
Medi# h#s to h#ve # pre-existing we#kness.
– Type A: more common #nd d#ngerous. proxim#l lesions, 1scending #ort#
– Type B: Not involving #scending #ort#, dist#l to the subcl#vi#n, less
d#ngerous.
– Signs begin #s strong p#in in #nterior chest r#di#ting to b#ck #nd progressing
down with dissection progress. Peric#rdi#l t#mpon#de is the most common
c#use of de#th (the dissection is close to the he#rt so the blood compresses
the he#rt). It c#n #lso go to the medi#stinum, compress other vessels #nd
more.
Thor1cic 1neurysm: B#llon like dil#tion of the thor#cic #ort#. #g#in you must
h#ve we#kness in the w#ll. Cl#ssic#lly is terti1ry syphilis. “tree b#rk”
#ppe#r#nce of #ort#.
Complic#tions: dil#tion of the #ortic v#lve root, compression of medi#stin#l
structures or thrombosis / embolism.
Abdomin1l Aortic Aneurysm: BELOW ren#l #rteries #nd ABOVE #ortic bifuc#tion.
Prim#ry due to #therosclerosis (thickening of intim#, which c#uses less oxygen
#rriving to dist#l p#rt of the w#ll, necrosis #nd w#ll we#kness #s # result), m#le
smoker #bove 60 with HTN. Puls#tile #bdomin#l m#ss th#t grows with time.
Complic#tion is rupture when gre1ter th1n 5 cm #nd then presents with
hypotension, puls#tile #bdomin#l m#ss #nd fl#nk p#in.

Shypilitic, gi1nt cell #nd T1k1y1su #re sometimes difficult to distinguish #nd
simil#r.

– Berry #neurysm: cerebr#l vessels outpouching th#t is due to congenit#l w#ll

we#kness.
– Arteriovenous fistul#s: #bnorm#l communic#tion between #rteries #nd veins.
Fistul#s c#n le#d to left-to-right v#scul#r shunting with incre#sed venous
return #nd high output he#rt f#ilure.
– Fibromuscul#r dyspl#si# is # foc#l irregul#r thickening of #rteri#l w#ll due to
hyperpl#smis of intim#te #nd medi# #nd fibrosis.
– Endotheli#l disfunction: #ltered phenotype th#t #ffects v#sore#ctivty.
– v#scul#r smooth muscles #re domin#nt p#rt of the vessel medi# #nd c#n
migr#te, prolifer#te, rele#se cytokines #nd GF, m#ke #nd remodel ECM,
constrict or dil#te.
– Intim#l thickening h#ppens #t the vessel reg#rdless of the injury type #nd the
neoihtim# is distinct from underlying medi#. in sm#ll-medium sized vessel
such neoihtim# c#n c#use stenosis.
– Peripher#l resist#nce is m#inly regul#ted #t the level of the #rterioles so their
influence on BP is highest.
– Aldosterone mut#tions: 11B-hydroxyl#se or 17#-hydroxyl#se mut#tions le#d to
incre#sed production.
 – Mut#tions in the ren#l epitheli#l N# ch#nnel protein le#d to incre#sed sodium
resorption (Liddle syndrome).
– Hy#line #rteriolosclerosis: endotheli#l cell injury, pl#sm# le#k#ge into
#rteriol#r w#lls #nd incre#sed SMC m#trix synthesis.
– Hyperpl#stic #rteriosclerosis: occurs in m1lign1nt hypertension. onion-skin
(look on slide) #rteriol#r thickening, reduplic#ted b#sement membr#ne #nd
SMC prolifer#tion, usu#lly with fibrin deposition #nd w#ll necrosis (necrotizing
#rteriolitis).. most common in kidney
– P#tterns of #rteriosclerosis: 1) Arteriolosclerosis: sm#ll #nd medium sized
#rteries #nd downstre#m ischemi#. 2) Monckeberg medi#l sclerosis: medi#l
c#lcific#tion in muscul#r #rteries usu#lly #fter #ge 50. non obstructive #nd
not clinic#lly signific#nt. 3) Atherosclerosis: most frequent #nd clinic#l
import#nt, l#rge to medium sized el#stic #rteries.

Shypilitic, gi#nt cell #nd T#k#y#su #re sometimes difficult to distinguish #nd
simil#r.

L1rge vessels

Tempor1l Gi1nt Cell 1rteritis

– Most common form of v#sculitis in older #dults #bove 50. C#rotid #rtery
br#nches #re most common, usu#lly tempor#l.
– Infl#mm#tory dise#se of blood vessels, sm#ll #rteries in he#d #nd neck
#ffected (#lso c#n be #ort# or ophth#lmic).. C#n c#use lose of vision, #ortic
#neurysms.
– c#uses thickening of v1scul1r w1ll #nd n1rrowing of lumen. T cell
medi#ted injury follows.
– He#d#che (tempor#l #.), Visu#l disturb#nces (Opth#lmic), J#w cl#udic#tion.
We will see flu like symptoms with joint #nd muscle p#in #nd elev#ted ESR.
– often gr1nulom1tous infl1mm1tion Develops with gi#nt cells, #s well #s
intim#l fibrosis. more fem#les th#n m#les (fever, f#tigue, weight lose,
he#d#che, p#int #long tempor#l #rtery, in 50% thereʼs ocul#r involvement.)
– A neg#tive biopsy wonʼt exclude the dise#se.
– Tre#tment is corticosteroids urgently, since irreversible blindness is # high risk
bec#use of the opth#lmic #rtery.
T1k1y1su 1rteritis
– B#sic#lly the s#me #s tempor#l gi#nt cell #rteritis, the difference is it h#ppens
in #dults below 1ge of 50, mostly young #si#n fem#le, #nd th#t is h#ppens in
the #ortic #rch #t br#nch points. c#using bisu#l #nd neurologic symptoms,
we#k or #bsent pulse in #n upper extremity , elev#ted ESR
– L#rge to medium sized vessels, #lso gr#nulom#tous v#sculitis, #lso ocul#r
disturb#nces.
– Compl#in on colder fingers, hypertension, neurologic deficits, cl#udic#tion
of legs, pulmon#ry hypertension. (pulmon#ry #rteries involved in 50% of
p#tients).
– M#rked intim#l thickening with sm#ll residu#l lumen. intim#te is thickened #nd
fibrotic, focus of necrosis in medi# with infl#mm#tory deposit.

Medium Vessels

Poly1rteritis nodos1
– Necrotizing v#sculitis involves most org#ns except the lung.
– systemic v#sculitis,, sm#ll-medium #rteries, involving kidney #nd sp#rring
pulmon#ry circul#tion. Sm#ll #neurysms 1ll over.
– M#inly in ren1l, c1rdi1c #nd viscer1l vessels. (NO #rterioles, c#pill#ries,
venules)
– mostly young #dults, with m#l#ise, fever, weight loss, #bdomin#l p#in #nd
melon. in 30% there is HBV Surf1ce Antigen #ntigen in serum. No ANCA
#ssoci#tion.
– Cl#ssic present#tion is hypertension, #bdomin#l p#in #nd bloody stool, diffuse
muscul#r #ches #nd p#ins.
– Ren#l involvement m#jor c#use of de#th.
– sm#ll vessel involvement is #bsent, glomeruli 1re sp1red, no GN.
– On im#ging, we see string-of-pe#rls #ppe#r#nce (Aneurysms) consists of
fibrinoid necrosis, then it gets fibrosed #nd feels like “node”, th#tʼs why
“nodos#”.
– Tre#tment #re corticosteroids.

K1w1s1ki dise1se (mucocut1neous lymph node syndrome)

– childhood v#sculitis, l#rge to medium vessels, 80% younger th#n 4.
– t#rgets coron1ry 1rteries with 20% of #neurysms formed.
– clinic#l presents with high fever, r#sh on p#lms #nd soles, lymph node
enl#rgement, erythem#, conjunctivitis.
– It is PAN-like. He#led lesions c#n c#use obstructive intim#l thickening.
– in contr#st to PAN, lung #nd kidney #re involved
– Thrombosis with myoc#rdi#l infr#ction #re # risk (since c#rdi#c #rteries #re
mostly involved. Aneurysms m#y form #nd rupture #s well.
– Tre#tment is Aspirin (protects vs thrombosis) #nd IVIG. Itʼs self limitied.
 –

Burger dise1se (Thrombo1ngiitis Obliter1ns)

– Young smokers. veins #nd extremities #re involved, T cell hypersensitivity.
– Affects digits in dist#l #rms #nd legs usu#lly, smoking induce #ntibodies
c#using infl#mm#tion.
– Sh#rply segment#l, thrombosing, #cute #nd chronic infl#mm#tion of medium
#nd sm1ll #rteries (tibi#l #nd r#di#l mostly), # thrombus occluded lumen with
# micro #ccess is common fe#ture. infl#mm#tion process extends to #ll l#yers
#nd nerves #nd eventu#lly encloses in fibrous tissue. L#te symptoms #re
chronic ulcer1tion of toes feet fingers #nd g1ngrenes. #bsence of smoking
import#nt.
R#yn#ud phenomenon is common in #bove dise#se: NOT v#sculitis. bec#use of
v#sosp#sms- p#roxysm#l cy#nosis. white, blue, red fingertips , toes, e#rs nor. two
forms: prim#ry or second#ry.
– Prim#ry more common in women.
– second#ry is in people older th#n 30, #s continu#tion of SLE, burger,
scleroderm# etc.

Sm1ll vessels

Gr1nulom1tosis with poly1ngiitis (Wegner “weCner” (C 1s 1 c going through

n1soph1ryns lung 1nd kidney 1nd reminding of C-ANCA, 1nd tre1tment is
cyclophosph1mide): GPA, necrotizing v#sculitis with the tri#d: necrotizing or
gr#nulom#tous v#sculitis, mostly in n1soph1rynx, lung #nd upper #irw#y #s well
#s kidneys (R#pidly Progressing glomerulonephritis 2) necrotizing gr#nulom#s of
upper #nd lower respir#tory tr#ct. 3) Glomerulonephritis. PR3-ANCA or C-ANCA
1re present in 95% of c1ses. Nodul#r infiltr#tes. typic#l p#tients 40 ye#rs old
m#le, bil#ter#l pneumonitis with nodules #nd c#vit#ry lesions, chronic sinusitis in
90%, n#soph#rynx mucos#l ulcer#tion in 75%, ren#l dise#se 80%, hem#turi#,
hemoptysis. On biopsy weʼll see l#rge necrotizing gr#nulom#s with v#sculitis.

Microscopic poly1ngiitis
– Necrotizing v#sculitis involving multiple org#ns, especi#lly lung #nd kidney.
– Simil#r to GW but n#soph#rynge#l involvement #nd gr#nulom#s #re #bsent
#nd thereʼll be P-ANCA r#ther th#n C-ANCA.
– Tre#tment is corticosteroids #nd cyclophosph#mide.

Chung Str1uss syndrome for sm1ll vessels

– looks like PAN but with eosinophili1. Necrotizing gr1nulom1tous v#sculitis
involving multiple org#ns, especi#lly lung #nd he#rt. The distinct symptoms
#re 1sthm1 #nd peripher#l eosinophil1.
 – P-ANCA levels correl#te with dise#se #ctivity. (like MP)

HSP (Henoch-Schönlein purpur#)

– V#sculitis due to IgA immune complex deposition.
– Most common v#sculitis in kids.
– P#lp#ble purpure on buttocks #nd legs.
– Gi p#in #nd bleeding, hem#turi# (IgA nephrop#thy), usu#lly they get it #fter
URT infection. (Since we gener#te lots of IgA during the infection which will be
deposited)

Mycotic #neurism: #rising from b#cteri#l infection of #rteri#l w#ll.

Bechet dise#se: sm#ll - medium vessel dise#se, neutrophil v#sculitis, usu#lly with
1) recurrent or#l #phthous ulcers, genit#l ulcers #nd uveitis.

Hem1ngiom1: Benign tumor comprised of blood vessels, commonly #t birth #nd

often regresses during childhood. Skin #nd liver #re most often involved.
Angios1rcom1: M#lign#nt prolifer#tion of endotheli#l cells, highly #ggressive.
common sites include skin, bre#st, liver. #ssoci#ted with PVC exposure, Arsenic
1nd Thorotr1st.
K1posi S1rcom1: Low gr#de m#lign#nt prolifer#tion of endotheli1l cells,
#ssoci#ted with HHV-8. Purple p#tches, pl#ques or nodules on skin, m#y involve
viscer#l org#ns. If you press on them they wonʼt explode. E#stern europe#n m#les
#re #t risk, #nd rel#ted with AIDS #nd tr#nspl#nt p#tients.