Path:
-@3-10wk GA, vasc endothelium arises fr mesenchymal cells that aggregate to --> blood islands (masses/cords)--> coalesc and disappear by absorption, and separate fr each other to --> discrete channels that evolve into the capillary bed
-pericytes and sm muscle cells surround the endothelium, derived fr neural crest (neuroectoderm),
-vasc bed differentiates into separate venous/arterial conduits to the capillaries
-Inherited vasc xx
-HHT- Hereditary hemorrhagic telangiectasia aka Osler-Weber-Rendu Syndrome (auto-Dom)
-Nl embryo dvp then they become abNl bc of structural weakness in the small art walls and precapillary sphincters--> congen abNly but ASx at birth
Classification:
-Hemangiomas = benign tumors of infancy w endothelial cell hyperplasia postnatally (prolif phase) and then regression over next 5-8yrs (involutive phase), no metastasis
-Malformations = xx in vasc morphogenesis, grow as child grows, w Nl rate of endothelial cell turnover
-Capillary, lymphatic, venous, arterial, or combo
-Fast flow = AV fistulas or AVMs
-Slow flow = capilary, venous, lymphatic
-can be in both systemic or pulm system
SYSTEMIC ARTERIAL MALFORMATIONS
-congenital or acquired
-Acquired p trauma, vascular puncture, arterial dysplasia (e.g. NF), atherosclerosis, syphilis, Wilmss tumor
Path:
-AVM =Arteriovenous malformation = microfistula - multiple art feeders joined at a nidus to draining vns
-AVF =Arteriovenous fistulas = macrofistulas - direct shunts bn large arterial and venous channels
-AVMs have no potenital for cellular prolif or involution (so they're diff fr hemangiomas),
-the arteries are dilated, tortuous, dysplastic w hyperplastic and disorganized medial sm muscle
-internal elastic lamina are fragmented/absent --> aneurysm and then rupture
-the veins are arterialized, bc of dysmorphogenesis or bc of incr intraluminal P
-have reactive muscular hyperplasia and then show degen changes- fibrosis, sm muscle atrophy, thrombi, then Ca'ion.
-usually single, or at single limb, but some may be multiple/multiorgan
-can have signif HD xx if in the brain, liver, chest, limbs
-HHT mainly affects skin, oral/nasal mucosa, lungs, CNS, GI, kidney, liver
-CNS AVM --> infant w CHF bc large AVF (e.g. vein of Galen) or superficial (pial), or dural
-if venous obstruction, then --> massive dilation, e.g. vein of Galen aneurysm
-may get cerebral ischemia fr vascular steal,
-may presnt as older infant/early child w hydrocephalus, sz, focal/general neuro Sx
-smaller AVM in brain parench can persist thru childhood, then p/w Si of cerebral/subarach hemorrhage, fr AVM or fr coexisting arterial aneurysm
-Thoracic AVM - IMA, w anomalous comm'n w mammary vns and ductus venosus
- SCA and innom vn
- intercostal arts and azygos vein
- axillary art and axillary vn
- carotid art and jugular vn
- RCA and R iliac vn via paravertebral plexus
- Desc Ao and azygous vn/SVC
--> CHF as early child if large
-Hepatic AVF- assoc w hemangioendotheliomas, rare to get high flow hepatic AVM w CHF
-if drain into portal vn, can --> GI bleed or other Si of portal htn
-Legs/pelvis -can--> CHF as infant
-if high flow AVM, get very big limb, w longer limb than unaffected limb
-Generalized extremity overgrowth of bn, muscle, fat..
-if low flow at the skin, common, must ddx venous/lymphatic vasc xx like Klippel Trenaunay syndrome.
-can do transcath embolization of discrete fistulas--> much improvement, but then new fistulas may dvp over time.
-may p/w limb gigantism, w atrophy of skin bc of venous ischemia
-mild-mod cardiac OD as child, more severe as adult
-Face/Neck- Q via external carotid art SCA, verebrals
-most p/w bleeding -dental/epistaxis, or w facial deformity
-large AVF may --> CHF as infant
-if arise fr vessels prox to Ao isthmus, may be assoc w preductal CoAo
-bc less Q thru isthmus in utero...
-Placenta/Chorioamnion--> fetal hydrops (fetal CHF) bc Q shunted away fr caudal Ao thru umbilical vn malformation, but cardiac failure improves as a neonate (rare lesion)
-Renal- rare, but assoc w Wilms tumor --> hematuria and htn
Physiology:
-L-->R --> vol OD the heart, and also local vascular insufficiency fr steal..., and compression or dilation of adjacent structures, and changes in vasc autoregulation
-SVR drops, so HR and SV incr, and plasma vol incr--> inr CO and wider PP
-incr venous return--> vol OD heart
-incr venous P + incr CO = High Output Heart Failure
-when heart no longer able to handle the bolume OD--> Low Output Heart Failure
-Incr in cardiac wk--> incr myocardial VO2, w relative ischemia bc low DBP, shortened diastoly fr tachycardia, +/- vascular steal
Sx/Si:
-d/o size, location, age
-neonate w system AVM/AVF, along w a PFO, PDA and incr PVR w relative RVH and decr RV compliance==> net R-->L at PDA and PFO, and incr venous return--> incr RAP to worsen R-->L at PFO
-so can present w cyanosis (70% pts) and CHF as neonate if large shunt
-mainly fr CNS, liver, Thorax AVM/AVF
-~ASx in utero bc placenta is also low resistant vasc bed...
-arteries proximal to the xx are big, pulsatile, w thrill &arteries distal to xx have Nl to diminished pulses
-cerebral xx- prominent carotid pulses, absent femoral pulses (DDx CoAo) bc much of the Q is going to lower resistant cerebral vasc bed and not the desc Ao...
-hyperdynamic heart, prominent S2, +S3or4, systolic murmur bc of TR or incr Q thru Ao/PA, and middiastolic murmur fr incr TV and MV Q
-systolic or continuous murmur at the AVM site bc of turbulent Q
-cranial bruits + in 30% of vein of Galen malformations
-if small shunting thru AVM/AVF, then later presentation, often w just a murmur or hyperkinetic circulatory state, of w pulsatile mass/thrill and continuous/systolic murmur at the malformation
-Nicoladoni-Branham's Sign = compress the afferent vessel w ur finger and murmur decreases/stops, HR slows, and arterial P increases, and vn P decreases
-may see local spontaneous hemorrhage or changes in local physiologic fx...
ECG- nonSp, check for signs of ischemia (ST/Twave...) and hypertrophy
CXR- cardiomegaly, pulm edema incr PA markings as neonate
-dilated desc Ao as an infant if hepatic xx
-older pt has mild CM or Nl CXR
Echo-
-r/o CHD, check ventricular size, hypertrophy/dilation, fx,
-big SVC (>Ao arch diam) and innominate vn--> c/s upper body shunt
-big IVC/hepatic vssls--> c/s hepatic/lower body shunt
-see turbulent, continuous Doppler venous Q instead of the Nl mainly diastolic flow pattern
-see dilated/tortuous Asc Ao/cephalic arts w intracranial/thoracic shunt
-Doppler- low velocity diastolic flow at carotids, w diastolic runoff at vessels distal to shunt...
-check for a PFO and PDA
Cath-
-not usually needed, but would show high output, incr atrial and ventric EDP, wide art PP, large diff in SO2 bn SVC and IVC (involved area has higher saturation...),
-incr PAP in neonates (bc LH failure)
CT/MRI- can help assess malformation...
DDx- must r/o CHD, CoAo, TAPVR, myocardial ischemia, CM, PDA, coronary AVF, ruptured sinus of valsalva aneurysm, AP window.
NHx & Tx:
-usually poor Px if large cerebral AVM, w 90% mortality by 1 WOL if no Tx, fr CHF and neuro xx (sz, intracranial hemorrhage), and survivors have signif neuro xx- hydroceph, intracranial hem., MR
-older pts w intracranial AVM get hemorrhage in >1/2, pk at teens, subarachnoid usually but can be intracerebral.
-hepatic vasc xx w/o Tx have 85% mortality as neonate
-if sev CHF, the only Tx is to reduce amt of shunting
-Must ddx hemangioma fr AVM/AVF- w US
-Must check for assoc xx like cerebral dysgenesis and excessive Ca'ion which may c/i xx Tx
-small Ca'ion may = ischemia--> must Tx quickly
-Surgery Tx if accessible and well circumscribed
-ligating it is only temporary solution bc other afferent arts will form
-Transcath embolization is now standard Tx
-AVMs still not curable bc very complex art supply and bc dvp new aff arts p Tx
-Vein of Galen malformation- up to 50% mortality for initial transcath embolization Tx, w survivors having sz, MR often, but both survival and xx are improved of late
PULMONARY ARTERIAL MALFORMATIONS
-most are congen or assoc w HHT
-acquired lesions assoc w juvenile hepatic cirrhosis, portal vn thrombi, trauma, schistosomiasis, metastatic thyroid CA, and pts w Glenn
-bc of exclusion of ? hepatic venous flow ("hepatic factor") directly to lungs
Path:
-mostly AVMs, structurally similar to systemic AVMs
-can degenerate w aneurysm formation--> rupture--> hemoptysis, hemoTx, pulmonary hemosiderosis
-2 Morph groups
-localized lesions - HHT, isolated pulm AVM
-diffuse- CHD pt, liver dz, portal vn thrombosis, Glenn pt
-small 1mm to huge tubular/saccular multilopulated structure taking up a whole lobe/lung (!)
-single or multiple, uni or bilat
-w Nl airways and lung parench surrounding the AVM
-AVM enlarges as child grows
-30-50% of pts w pulm AVMs have HHT
Physiology:
-R-->L shunting --> systemic desat and polycythemia
-no change in CO (unlike systemic AVMs), and plasma volume stays Nl. as does pulm pressures, w Nl PVR
-resistance by AVM is low, but at other lung segments may be elevated by 2x...
-so Q preferentially to the AVM over other lung parts, but net no PVR change
-emboli and bact can pass directly thru AVM--> risk of stroke and brain abscess
-many pts have Orthodeoxia = desat w sittting/standing, bc of basal location of most pulm AVMs so w gravity there is more Q to base of lung--> more R-->L shunting
Si/Sx:
-correlate w shunting- cyanosis, clubbing, polycythemia by early adult
-can have cyanosis + CHF as neonate
-less obvious in older pt w HHT bc of anemia due to bld loss
-Sx- DOE, hemoptysis, hemoTx
-some get CP w AVM rupture--> hemoTx
-endarteritis
-neuro - HA, sz, speech d/o, ocular changes, transitory numbness
-paradoxical emboli--> TIA, stroke (1.5%/yr stroke risk, in total 37% TIA, 18% stroke), cerebral abscess, often p dental procedure
-HHT Sx- nosebleed, hemoptysis, hematuria, vag/GI hemorrhage
-Exam- Nl pulse and precordial activity and hrt sounds; 1/2 w faint syst/cont murmur at the lesion if big enough that incr w deep inspiration bc incr Q
ECG- Nl in most, may have LAE, LVH if direct commn bn RPA and LA
CXR- usually Nl heart size, CM only if very big, see lobulated opacities sometimes, +/- Ca'ion
Echo- can inject periph vn contrast and see it get to RA/RV and then after a few beets to LA/LV
Cath- check pulm vn SO2- affect lung segments will have desaturated pulm vns unresponsive to FiO2
-Angio- ID AVMs- see dilated/tortuous aff and eff vessels, early LA opacification, scarce opacification of uninvolved areas of the lung
-Pts w CHD tend to have smaller more diffuse AVMs, so u see rapid pulm vn filling...
CT/MRI- can help delineate AVMs...
NHx & Tx:
-most pts ASx as infant/child, but if +Sx very hard to Tx
-if present as infant, than poor Px bc it's usually sev, and high risk of xx, so elect to Tx early
-Tx w transcath embolization w coils
-Surgical Tx w lobectomy/pneumonectomy done initially in 1940s, but today a 5% operative mortality but 75% cure rate; xx = chest wall deformity in infant/child and changes in lung mechanics
HEMANGIOMAS
Epi:
-40% are able to be seen at bith
-grow over 1st 6-12mo old, then involute over several years
-rarely do they cause enough shunting to cause cardiac xx
-F>M 3:1
Path:
-cellular prolif, unlike AVM/AVF
-->large cellular mass, needs recruitment of new feeding/draining vasc channels
=mass of endothelial cells +/- vasc lumen
-at prolif stage, the grow rapidly, w incr mast cell [ ]. w multilaminated basement membrane
-at involuting stage, see fibrofatty infiltration, normal mast cell [ ]. then gets more organized, into lobular compartments, seprated by fibrous septa, and w large feeding/draining vssls
-end stage of involuation- has thick/tin walled vssls that look like capillaries
-b-FGF (fibroblast growth factor) can be trended to see response to Tx
-Hepatic hemangiomas/hemangioendotheliomas- can --> CHF if +fistula also
-often w cutaneous hemangiomas too
-Pulmonary- rare, heterogenous xx- ...,
-Sx/Dx are similar to AVMs d/o location etc, but rarely --> xx
-Kasabach-Merritt syndrome = consumptive coagulopathy of pltlts +/-fibrinogen (rare xx at prolif stage)
Cath:
-ddx by angio- well circ mass w intense, persistent tissue staining, organied in a lobular pattern while AVMs are diffuse lesions w many tortuous, enlarged, irregular vssls w/o intervening tissues tain
-may be hard to ddx AVM fr a high flow hemangioma
-hepatic lesions are unique and ddx AVM bc these hemangiomas have fistulas and cavernous dilations of draining vns, multiple sources of collat supply, uncommon elsewhere in body for hemangiomas
NHx & Tx:
-usually benign
-if grow too fast can cause lifethreatening xx- CHF, hemorrhage, soft tissue destruction, deformed obst to vital structures, sepsis
-so Tx if life threatening Sx
-transcath embolization,
-radiation, cyclophosphamide Tx less effective and has xx
-IFN-a2a is new Tx w good results (but major xx if AVM/AVF bc it can diminish the single endothelial layer and cause hemorrhage)