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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3734_Библиотеки_им_академика_М_И_Перельмана
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Aortic Anatomy andthePathophysiology ofAcute Aortic Syndromes
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subclavian may compress the esophagus resulting in dysphagia lusoria. The left
vertebral artery may also originate from the arch independent of the left subclavian
artery in 3–4% of people [4].
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Right Aortic Arch
A right-sided aortic arch is marked by an arch that crosses anterior to the right pulmonary bronchus (Fig. 4d). This occurs in less than 1% of the population. The
anomaly is due to persistence of the right fourth pharyngeal arch in combination
with regression of the left fourth pharyngeal arch and of the eighth dorsal aortic
segment. The descending aorta usually runs to the right of the spine but may course
on the left side. Vascular rings may result from incomplete regression and may
cause compressive symptoms.
Double Aortic Arch
Persistence of both the right and left fourth pharyngeal arches in addition to the
dorsal aorta results in a double aortic arch (Fig.4e). Each arch serves as the origin
for the ipsilateral carotid and subclavian arteries. The arches themselves may either
be patent or atretic. The right arch typically extends more superiorly and posteriorly
and is larger than the left. As this represents a true vascular ring, compressive symptoms may develop from obstruction of the trachea and/or esophagus.
Aortic Coarctation
Aortic coarctation is found more frequently than many of the aforementioned arch
anomalies, accounting for approximately 5% of congenital heart disease diagnoses.
Focal hyperplasia of the aortic media results in narrowing near the location of the
fetal ductus arteriosus. Coarctation is associated with bicuspid aortic valve, Turner
syndrome and ventricular septal defect. More severe lesions often present in infancy,
however, development of collateral vessels may render this partial obstruction
asymptomatic until incidentally detected in adulthood. In rare cases, coarctation
may occur more distally in the descending thoracic aorta.
Histology oftheAortic Wall
Appreciation of the microscopic structure of the thoracic aortic wall helps to contextualize the thoracic aortic pathologies and the natural history of relevant disease
processes that will be described in the following sections. Like other arterial
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Adv
Vasa vasorum
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L. V. Huckaby and T. G. Gleason
entitia
Media
Intima
External
elastic lamina
Internal
elastic lamina
Lumen
Endothelial cell
Smooth muscle cell
Fibroblast
Elastin
Collagen
Fig. 5 Composition of the aortic wall. The outermost layer, the adventitia, consists of a collagenbased strength layer and provides blood supply to the aortic wall through the vasa vasorum. The
aortic media is comprised of smooth muscle cells (SMCs) with structural extracellular matrix
(ECM) components and the external elastic lamina. The intima is composed of an endothelial
monolayer, connective tissue and the internal elastic lamina
structures, the aortic wall consists of three layers which, from the lumen moving
outwards, are termed the intima, media and adventitia (Fig.5).
The innermost layer, the intima, can be further subdivided into the single cell
layered endothelium and subendothelial connective tissue. Endothelial cells mediate signaling between the lumen and the deeper layers of the aortic wall. For example, endothelial cells, in response to mechanical and biochemical signals, may
inuence the function of aortic smooth muscle cells in the medial layer. The intimal
layer receives its blood supply via diffusion from the aortic lumen, which is also the
source of oxygen and nutrients for the innermost portions of the medial layer. The
internal elastic lamina, a fenestrated sheet of elastic bers, separates the intimal
layer from the media.
Aortic Anatomy andthePathophysiology ofAcute Aortic Syndromes
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The medial layer has been a focus of investigation since Austrian pathologist
Jakob Erdheim rst described “medionecrosis aortae idiopathica” in 1929 [5].
While the exact pathogenesis of medial changes leading to aortic aneurysm or dissection have been debated since that time, there is no doubt that the thoracic aortic
media plays a key role in both normal physiology as well as in pathophysiologic
states. The media is the thickest of the three layers. Aortic smooth muscle cells
(SMCs) constitute the main cell type and function to maintain the structural integrity of the aortic wall. Particularly important for aortic aneurysm pathophysiology,
they are responsible for regulation of the extracellular matrix (ECM), consisting
mainly of the brillar proteins collagen and elastin. Intact collagen bers and elastin
bers, organized into elastic lamellae, confer strength and resist hemodynamic
forces; fragmentation of these bers is seen in diseased aortas, similar to that historically described as cystic medial necrosis. Fibrillin-1 is an essential component
of the ECM, critical to organized elastin deposition, and mutations of this gene are
responsible for the Marfan syndrome. The outermost portion of the media is delineated by the external elastic lamina.
The adventitia is the outermost layer of the aorta and contains the vasa vasorum,
or blood vessels of the blood vessel. The vasa vasorum supplies the adventitia and
outer portions of the media which do not receive sufcient blood supply via diffusion from the aortic lumen. In this layer, broblasts are the main contributing cell
and are responsible for production of collagen bers, mainly type I and type III,
which constitute a majority of the volume of the adventitia. A layer of periadventitial fat often surrounds the three-layered vessel wall and may itself secrete paracrine
factors which regulate aortic function, though investigation into its role is ongoing.
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Thoracic Aortic Aneurysm
Dilatation of the aortic wall may be associated with heritable aortopathies, but more
commonly is degenerative in nature and is therefore associated with aging. While
often clinically silent and frequently diagnosed incidentally, thoracic aortic aneurysm (TAA) connotes an associated risk of aortic catastrophe, i.e. aorta dissection
and/or rupture. Characteristics common to TAA of all etiologies include focal or
global aortic wall integrity loss manifesting as saccular or fusiform aortic
enlargement.
Aside from the heritable causes of TAA which are discussed in subsequent sections, risk factors for TAA include hypertension, smoking, age, and sex. Medial
degeneration is the predominant histologic feature and may be driven by local cellular perturbations or result from the failure of the aortic wall to appropriately adapt
and respond to physiologic hemodynamic forces (Fig.6a–b). A systematic review
of TAA growth identied larger diameter and distal aneurysmal disease as risk factors for accelerated aortic growth with an average growth rate of 0.2–4.2 mm/
year [6].
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L. V. Huckaby and T. G. Gleason
Histologic features in descending thoracic aortic aneurysms often demonstrate
the coexistence of atherosclerotic disease, which is not thought to be a driving factor
in the pathogenesis of TAA in the ascending aorta. Extent of thoracoabdominal
aneurysms follows the Crawford classication (with Sa modication): type 1
includes aneurysms originating distal to the left subclavian and terminating proximal to the renal vessels, type 2 extends the zone covered by type 1 to the aortoiliac
bifurcation, type 3 involves aneurysms originating in the distal descending aorta
Fig. 6 Histology of the
diseased aortic wall. Graphic
depictions of normal (a) and
aneurysmal (b) histology of
the aortic wall are shown.
Thoracic aortic aneurysm has
historically been
characterized by medial
degeneration, consisting of
the classic ndings of smooth
muscle cell (SMC) apoptosis,
proteoglycan accumulation
and extracellular matrix
degradation
Smooth muscle cell
Elastin
Collagen
b
Proteoglycans
Matrix
metalloproteinase
enzyme
lumen
lumen
sation
abcd
Aortic Anatomy andthePathophysiology ofAcute Aortic Syndromes
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that extend to the aortic bifurcation, type 4 involves only the abdominal aorta with
aneurysm originating at or around the mesenteric arteries extending to the aortic
bifurcation, and type 5 aneurysms involve the distal descending aorta from around
the sixth thoracic vertebrae to the mesenteric arteries [7].
Penetrating Atherosclerotic Ulcer andIntramural Hematoma
Improvements in radiologic technology, particularly computed tomography (CT),
have expanded the spectrum of aortic pathologies that must be risk-stratied and
appropriately managed. Penetrating atherosclerotic ulcer (PAU) is one such nding
that was previously only detected histologically (Fig.7a). PAU begins as an atheromatous plaque and progresses to ulceration of the intima with disruption of the
internal elastic lamina and may lead to hematoma formation within the media. It
PAU IMH Dissection Rupture
Fig. 7 Spectrum of acute aortic processes. Penetrating atherosclerotic ulcer (PAU), intramural
hematoma (IMH) and acute aortic dissection (AAD) constitute radiologic and gross ndings of
acute aortic syndromes. PAU (a) represents ulceration of an atherosclerotic plaque into the medial
layer. IMH (b) results from hemorrhage within the medial layer in the absence of intimal disruption. Aortic dissection (c) occurs when an intimal tear permits blood ow through a false lumen
within the medial layer. Rupture of the aortic wall (d) may also occur these entities
Clot
False
Tr ue
Extrava
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may progress to intramural hematoma (IMH) formation, aortic dissection/rupture,
or result in pseudoaneurysm formation. The majority of PAUs are located in the
descending thoracic aorta [8].
In contrast, IMH can result from rupture of the vasa vasorum within the media
creating focal accumulation of blood in the wall in the absence of a direct communication to the lumen (Fig.7b). IMH may be present with concurrent PAU and may
progress to frank aortic dissection in 28–47% of cases [8]. Spontaneous resolution
of IMH has also been reported. IMH location is also important with those found in
in the ascending aorta necessitating urgent operative intervention due to a higher
risk of dissection or rupture.
L. V. Huckaby and T. G. Gleason
Aortic Dissection andRupture
Aortic catastrophic, thoracic aortic dissection and/or rupture constitute the
sequelae of terminal structural failure of the aortic wall (Fig.7d). Aortic dissection is dened by local intimal disruption permitting blood ow through a false
lumen within the medial layer. Longitudinal propagation through this false lumen
and resulting compression of the true lumen may compromise perfusion to the
arch vessels at their origins and dissection can continue to propagate distally both
along arch vessels and down the descending aorta. Aortic dissection has been
classied based on the extent of involvement by the Stanford and DeBakey
schema. Stanford type A describes any involvement of the ascending aorta
whereas type B is exclusively localized to the descending aorta (Fig.8a). DeBakey
type I involves both ascending and descending thoracic aorta while types II and
IIIA describe exclusive involvement of the ascending and descending thoracic
aorta, respectively; type IIIB is characterized by dissection in the descending and
abdominal aorta (Fig.8b).
Approximately 67% of all acute aortic dissections are type A, with two-thirds of
dissection patients being male; the average age of presentation is 63 years [9].
Presence of hypertension as well as pre-existing aortic dilatation are signicant risk
factors for dissection. Although aortic diameter may correlate to some extent with
intrinsic wall weakening, a majority of patients who experience aortic dissection
have diameters below the surgical threshold of 5.5cm for elective aneurysm repair
[10]. Quantication of focal mechanical stresses on the aortic wall may improve
understanding of individualized risk, particularly in those patients with smaller aortic diameters [11, 12].
Aortic rupture results from full thickness failure of the aortic wall and may be
preceded by PAU, IMH or dissection, indicating a sequence of failure of the adventitia to contain the blood after the initial pathologic insult. True incidence is unknown
due to the propensity for sudden death. Contained rupture into the pericardium may
result in tamponade while free rupture into a pleural cavity often leads to rapid,
lethal exsanguination.
ab
Stanford
Debakey
Aortic Anatomy andthePathophysiology ofAcute Aortic Syndromes
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I II IIIa IIIb
Fig. 8 Dissection classication. Aortic dissection involving the ascending and/or descending thoracic aorta is classied using the Stanford (a) or DeBakey (b) schema which each delineate areas
of involvement
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Special Cases
Iatrogenic
Iatrogenic aortic injury has been associated with both open and percutaneous interventions. Spinal hardware, commonly vertebral pedicle screws, may encroach upon
the descending aorta causing dissection in an acute or delayed fashion. Resulting
injury ranges from acute or delayed perforation, which may occur years later, or
pseudoaneurysm formation [13, 14]. The natural history of screws abutting but not
penetrating the aorta is unknown, however, the high mortality rates of vascular complications of spinal procedures suggest consideration of screw removal [15].
Despite quick recognition and appropriate management, iatrogenic type A dissection associated with open heart surgery carries a high mortality rate of 40% [16].
A retrospective review by Ahn etal. found an incidence of 0.29% among cardiac
surgery cases with the aortic tear related to the cannulation site in 9 of 10 cases [16].
Of those patients with available pre-operative CT imaging, ascending aortic size
ranged from 31 to 55mm, however, the low sample size precluded analysis of risk
factors for injury resulting in dissection.
In addition to open surgery, interventional procedures harbor a low but notable
risk of aortic injury. Aortic dissection following percutaneous coronary intervention
is rare, with an incidence of 0.06% in one series, but is often detected immediately
and thus associated with relatively low mortality [17]. Retrograde type A dissection
may occur secondary to endovascular stenting of the descending aorta. In one
report, retrograde dissection occurred in 1.9% of patients undergoing TEVAR [18].
All cases were associated with placement of the proximal extent of the graft in the
ascending aorta or arch and incidence was increased among those with an aortic
diameter of greater than or equal to 4.0cm [18].
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L. V. Huckaby and T. G. Gleason
Blunt Trauma
Traumatic aortic rupture may occur with blunt chest trauma and is most commonly
seen with sudden deceleration, such as motor vehicle accidents. Insult to the aortic
wall is most commonly localized to the aortic isthmus near the ligamentum arteriosum, which may serve as a rigid point of xation allowing a shearing effect on the
surrounding aorta. Alternatively, clinical data supports the so-called “osseous pinch”
theory whereby the aorta is directly sheared between bony structures of the anterior
thoracic (manubrium, rst ribs and clavicular heads) and the posterior vertebral column [19, 20]. While approximately two-thirds of injuries occur at the isthmus, the
ascending and more distal descending thoracic aorta can also be at risk. Rupture is
thought to occur in a stepwise fashion with the traumatic insult rst generating a tear
in the intimal/medial layers which progresses to full thickness rupture, thus providing
a potential window of opportunity for intervention [21]. Although the true incidence
is unknown, in one study 35% of trauma victims undergoing autopsy showed evidence of traumatic thoracic aortic injury, of whom 80% died at the scene [22]. Given
the spectrum of aortic injury severity, radiologic imaging may reveal injuries less
prone to rupture, such as isolated intimal disruptions or small pseudoaneurysms, yet
risk stratication for such ndings in the context of trauma has not been fully dened.
Pregnancy
Pregnancy may predispose individuals to highly morbid vascular phenomena, such as
the risk of splenic artery rupture, hemorrhagic stroke, and aortic pathologies. Both hormonal uctuation and hemodynamic changes have been proposed as potential risk factors. Pregnancy-associated aortic catastrophe in Marfan syndrome (MFS), the most
common heritable aortopathy, has received the most attention. A retrospective review of
98 women with MFS revealed increased aortic growth rate during pregnancy with an
overall increased risk of dissection and elective repair on long-term follow-up compared to nulliparous MFS women [23]. In this cohort, no women experienced aortic
events during pregnancy. However, those MFS patients with pre-existing risk factors for
aortic dissection, such as aortic diameter greater than 40mm, appear to be at a heightened risk for experiencing an aortic event during pregnancy [24]. Among the general
population, aortic dissection and rupture remains elevated during pregnancy, as demonstrated by a study of over six million pregnant and postpartum women [25]. Nevertheless,
the occurrence is rare though caution must be exercised in those with known aortopathy.
Cocaine Use
Use of cocaine has been linked to acute coronary syndrome and arrhythmia and
has anecdotally been associated with acute aortic dissection in a younger population than that seen with degenerative TAA and dissection. In a retrospective
Aortic Anatomy andthePathophysiology ofAcute Aortic Syndromes
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review of patients who experienced dissection comparing those who did and did
not use cocaine, dissection location and extent did not appear to differ [26]. These
patients presented at an average of 12.8h after substance ingestion [26]. Cocaine
functions as a sympathomimetic, raising intracellular calcium and leading to transient tachycardia and hypertension. Given the temporality between substance
ingestion and symptomatic presentation, it is plausible that acute changes in blood
pressure may incite intimal tear and subsequent dissection. The relative contribution of repetitive cocaine usage on aortic wall pathology has not yet been
investigated.
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Bicuspid Aortic Valve Aortopathy
The most common congenital heart defect, affecting 1–2% of the population, is a
bicuspid aortic valve (BAV). While characterized by its valvular morphology,
BAV is strongly associated with an ascending aortopathy with a majority of BAV
patients having a larger diameter ascending aorta compared to age- and sexmatched controls with many (up to 84%) developing aneurysmal features [27,
28]. Two hypotheses have been proposed to relate concomitant valve disease and
aneurysm: one posits that dilatation results from an intrinsic aortic wall defect,
possibly related to similar embryologic origins as the valve tissue, and the other
implicates altered blood ow through the bicuspid valve with eccentric jets creating focal strain on the ascending aortic wall. To date, no singular genetic mutation
has been ascribed to the presence of BAV, although its heritability is understood
[29, 30]. Various mechanisms for BAV aortopathy have been proposed including:
multifactorial genetic contributions, defective cellular response to oxidative
stress, alterations in extracellular matrix remodeling, and modied epigenetic
control [31–34]. By 30years of age, over half of BAV patients demonstrate aortic
dilatation and the prevalence increases to 88% for those over 60 [35]. The relative
risk of aortic dissection in patients with TAA associated with BAV, in comparison
with those with TAA and a normal aortic valve, is similar [36], although this topic
of relative risk has been controversial. Further studies will be necessary to identify BAV-specic risk factors for aortic dissection and thereby direct decisions for
elective aortic replacement.
Inherited Aortopathies
Marfan Syndrome
First described in 1896 by Antoine Marfan, the Marfan syndrome (MFS) is the most
common known genetically-triggered aortopathy and is marked by early and extensive TAA and aortic dissection. Phenotypic manifestations include ectopia lentis,
tall stature, and arachnodactyly. Pathogenesis is linked to a mutation in the ECM
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structural protein brillin-1, which regulates transforming growth factor (TGF)-β
signaling. A spectrum of disease is seen that appears to relate to the specic mutations seen involving brillin-1 giving rise to some but not all MFS features in some
patients, so-called Marfan forme fruste. Aortic disease, the primary cause of early
death among MFS patients, is characterized by a root phenotype, with enlargement
of the sinuses of Valsalva, and occurs in 15–44% of patients [37]. Involvement of
the root has been attributed to alterations in elastin content with resultant tissue
weakening under physiologic hemodynamic forces [38]. Aortic disease, however, is
not limited to the root. Examination of long-term outcomes in MFS patients by Kari
etal. revealed that 68% of dissections were DeBakey type I, which paralleled their
ndings of high rates of reintervention for descending aortic disease [39].
Histologically, features of cystic medial degeneration are seen although this is not
pathognomonic.
L. V. Huckaby and T. G. Gleason
EDS
Multiple subtypes constitute Ehlers-Danlos syndrome (EDS), however, type IV, the
vascular subtype, is most commonly associated with thoracic aortic disease.
Characterized by a defect in the COL3A1 gene encoding type III procollagen, the
EDS type IV phenotype consists of predisposition to bowel, uterine and arterial
rupture in addition to characteristic facial features and thinned skin with visible vessels. Inheritance is autosomal dominant. Patients with EDS experience early death
at a mean age of 50years with the majority of these being attributable to arterial
rupture [40, 41]. Widespread medium and large vessel involvement is typical in
EDS with a complication involving the aorta leading to death in 68% of cases [40].
Animal models of COL3A1 haploinsufciency demonstrate aortic dissection in the
absence of aneurysm and with associated decreases in medial collagen content [42].
Owing to the high risk of sudden death and the rarity of the EDS, there is a lack of
knowledge about the natural history of thoracic aortic disease and of the histologic
ndings in those who undergo resection. Nevertheless, these clinical manifestations
highlight the importance of collagen type III in maintaining extracellular matrix
function in the aorta.
LDS
Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder rst described in 2005 that results from a genetic mutation in TGF-β or its
receptor [43]. Fibrillin-1, which is mutated in MFS, binds TGF-β thus regulating
downstream signaling including TGF-β receptor-mediated pathways. Similar
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