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Glycoprotein
Degenerated
Degenerated
lamellae
normal appearing
3 Pathophysiology ofAscending Aortic Aneurysm andDissection
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Fig. 3.7 Ascending
aneurysm formation. Most
aneurysms develop over time
and are associated with
microstructural changes in the
aortic media. In normal elastic
lamellae under normal blood
pressure conditions, collagen
bers are slack, and elastic
bers carry the load. The
normal microstructure
includes elastic ber
extensions between the loaded
lamellae and SMCs to provide
mechanosensation and
mechanotransduction. With
inappropriate signaling and
uncoupling of SMCs, there
are matrix degradation,
apoptosis of SMCs, and
elastolysis. An intermediate
stage exists where elastic
lamellae may persist without
SMCs. The ultimate result is
that areas of the media lose
functional elastic bers and
have no elastic recoil.
Collagen bers are tensioned,
and the aortic diameter
necessarily increases, and the
wall thins. Tears that may lead
to dissection occur in the
more normal-appearing areas
such as on the lower left
Tears occur in
SMCs with
elastic
extensions
Elastic lamellae
areas
Collagen bundles
not under tension
load born by elastic
SMC
pool
37
elastin
Collagen bundles
now load bearing
Smooth lamellae
with no SMCs
Loss of elastic
extensions
7. Impairment in canonical TGFβ signaling is a cause of
8. Loss of mechanosensation or mechanotransduction by
9. The nding of microscopic transverse tears in the media
A large proportion of ascending aneurysms have a recognizable genetic defect that promotes this process.
Those defects associated with preservation of robust
collagen bers are likely to present later in life with
larger aneurysms but remain subject to the mechanical
features of the degenerated 6cm aorta. This group may
represent the majority of patients with aneurysms
(Fig.3.7).
aneurysms. Upregulation of noncanonical TGFβ signaling, possibly in response to decient canonical pathways, may be the driving factor.
SMCs with loss of elastic ber extensions to elastic
lamellae likely plays a major role in the pathogenesis of
both aneurysm and dissection.
of “normal” aortas may indicate the presence of a subclinical defect but also illustrates the dangers of uncontrolled hypertension where such a tear could provide a
nidus for dissection. Aneurysm and dissection are both
diseases of hypertension.
10. Accurate prediction of rupture and dissection requires
knowledge of the expected micromechanical properties
of a patient’s aorta as well as a precise morphologic
characterization. High-resolution, dynamic imaging
combined with genomic testing could result in improved
prediction methods.
Syndromic andNonsyndromic Ascending
Aortic Disease
Syndromes of thoracic aneurysms and dissection, known as
TAAD, have a strong genetic component and, when inherited
by more than one member of a family, are often referred to as
familial TAAD (FTAAD). Descending thoracic aortic pathology is associated with hypertension and known risk factors
for atherosclerosis. While these risk factors may play some
38
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Table 3.1 Catalog of genetic syndromes involving the ascending aorta
Gene Locus Altered protein Syndrome Inheritance
ECM proteins
FBN1 15q21.1 Fibrillin-1 Marfan syndrome AD
EFEMP2 11q13.1 Fibulin-4 Cutis laxa type IB AR
ELN 7q11.23 Elastin Cutis laxa AD
COL3A1 2q32.2 Collagen 3 alpha-1 Ehlers-Danlos syndrome type 4 AD
COL4A1 13q34 Collagen 4 alpha-1 Hereditary angiopathy with nephropathy, aneurysms,
COL
4A5
PLOD1 1p36.22 Lysyl hydroxylase 1 Ehlers-Danlos syndrome type 6 AR
PLOD3 7q22 Lysyl hydroxylase 3 Bone fragility, contractures, arterial rupture, deafness AR
LOX 5q23.1 Lysyl oxidase FTAAD, (AAT10) AD
MFAP5 12p13.31 Microbrillar associated protein 5
TGFβ pathway proteins
TGFBR1 9q22.33 Transforming growth factor beta
TGFBR2 3q24.1 Transforming growth factor beta
TGFB2 1q41 Transforming growth factor beta 2 Loeys-Dietz syndrome type 4 AD
TGFB3 14q24.3 Transforming growth factor beta 3 Loeys-Dietz syndrome type 5 AD
SMAD2 18q21.1 SMAD family 2 Aortic/peripheral arterial aneurysm/dissection
SMAD3 15q22.33 SMAD family 3 Aneurysms-osteoarthritis syndrome/Loeys-Dietz
SMAD4 18q21.2 SMAD family 4 Juvenile polyposis/hereditary hemorrhagic telangiectasia AD
SKI 1p36.33-p36.32 SKI sarcoma oncogene homolog Shprintzen-Goldberg syndrome AD
Smooth muscle contractile unit proteins
ACTA2 10q23.3 Smooth muscle cell alpha actin FTAAD (AAT6) Moyamoya disease AD
MYH11 16p13.11 Smooth muscle cell myosin heavy
FLNA Xq28 Filamin A Periventricular nodular heterotopia X-linked
MYLK 3q21.1 Myosin light chain kinase FTAAD (AAT7) AD
PRKG1 10q11.2 cGMP-dependent protein kinase
Neural crest migration
NOTCH1 9q34.3 Notch1 Bicuspid aortic valve with aneurysm AD
Undened defect
Data from: Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University
(Baltimore, MD). Updated October 19, 2017. World Wide Web URL:
Xq22.3 Collagen 4 alpha-5 X-linked Alport syndrome X-linked
(MAGP-2)
receptor 1
receptor 2
chain
type 1
11q23.3–24 FTAAD (AAT1)
5q13-q14 FTAAD (AAT2)
muscle cramps (HANAC)
FTAAD, (AAT9) AD
Loeys-Dietz syndrome type 1, (AAT5), AD
Loeys-Dietz syndrome type 2, (AAT3) AD
syndrome type 3
FTAAD (AAT4) AD
FTAAD (AAT8) AD
https://omim.org/
AD
AD
dominant
role in the development of ascending aortic pathology,
genetic factors appear to play a larger role. The genetic
aspects of ascending aortic pathology can be categorized as
syndromic and nonsyndromic. The term syndromic refers to
phenotypes of the genetic defect that involve other organ systems as well as the cardiovascular system and occur in recognizable patterns. Nonsyndromic defects appear to be
primarily manifested within the aorta or occur as sporadic
cases. Syndromic aortic defects are more easily recognizable
clinically and include Marfan syndrome (MFS), Loeys-Dietz
syndrome (LDS), Ehlers-Danlos syndrome type 4 (EDS-IV),
Weill-Marchesani syndrome (WMS), aneurysm arthritis
syndrome, arterial tortuosity, and cutis laxa [91] (Table3.1).
Marfan syndrome is an autosomal dominant disorder of
connective tissues most commonly due to a mutation in the
FBN1 gene encoding for the protein brillin 1. Penetrance is
100%, but the phenotype can be variable. The phenotype
typically consists of skeletal abnormalities such as pectus
excavatum or carinatum, arachnodactyly, scoliosis, increased
joint laxity, mitral valve prolapse, ectopia lentis, striae of the
skin, and dural ectasia. The most deadly phenotypic manifestation of this disorder is found in the dilation and degenerative changes of the aortic root and ascending aorta, which
can lead to dissection and rupture.
Fibrillin mutations also are associated with the WeillMarchesani syndrome. While brillin mutations in MFS
3 Pathophysiology ofAscending Aortic Aneurysm andDissection
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39
cause tall stature, arachnodactyly, hypermobile joints, and
hypomuscularity, the opposite phenotype appears in WMS
[49]. WMS patients have short stature, brachydactyly, stiff
joints, ectopia lentis, myopia, glaucoma, tight skin, hypermuscularity, and heart defects. WMS can be inherited in an
autosomal dominant or recessive fashion. The recessive type
has been linked to a gene on chromosome 19. ADAMTS10,
a zinc-dependent protease, has been linked to autosomal
recessive forms of WMS.The autosomal dominant form has
been linked to the FBN1 gene. Cardiovascular defects that
affect people with WMS include mitral valve prolapse, aortic
and pulmonary valve stenosis, ventricular septal defects,
QTc prolongation, and ascending aortic dilation [91, 92].
Loeys-Dietz syndrome is associated primarily with TGFβ
signaling pathways. Patients with LDS inherit the phenotype
in an autosomal dominant pattern and have chest wall deformities such as pectus carinatum or pectus excavatum, a high
arched or cleft palate, pes planus, clubfoot, scoliosis, bid
uvula, hypertelorism, widespread arterial tortuosity, and specically aortic root aneurysms. They are similar in phenotype to MFS patients, except that the arteriopathy that occurs
in LDS seems to be more widespread and occurs in peripheral arteries as well as the aorta. There are ve types of
Loeys-Dietz syndrome. Type 1 is caused by mutations in the
TGFBR1 gene, which encodes for the TGFβ receptor 1. Type
2 is caused by mutations in TGFBR2 [93]. Type 2 patients
tend to have joint laxity, easy bruising, velvety skin, diffuse
arterial aneurysms and dissections, and near translucent skin
[94]. Type 3 mutations are caused by mutations of the
SMAD3 gene. Type 4 LDS is caused by a mutation involving
the TGFβ 2 ligand [93]. Type 5 LDS is caused by a mutation
in the gene encoding for TGFβ 3 ligand. As with MFS, the
greatest clinical danger with LDS is the presence of severe
cardiovascular defects. LDS is associated with aortic dissection, occasionally with no warning and no apparent dilation.
The mean age of rst vascular events tends to occur at a
younger age, at around 30years old.
Vascular Ehlers-Danlos syndrome type 4 (EDS-IV) is a
connective tissue disorder that affects type 3 collagen. There
are more than ten types of EDS, each with a different phenotype. Most phenotypes share similarities in regard to joint
hypermobility, cutaneous fragility, and hyperextensibility.
Type 4 is generally an autosomal dominant inherited disorder although autosomal recessive forms have also been
described. There is signicant phenotypic overlap between
LDS and EDS-IV.EDS-IV patients are often short and have
translucent skin. Their joint hyperextensibility is less pronounced than other EDS types. In addition to frequent arterial rupture, EDS-IV patients are found to have valvular
prolapse and frequent spontaneous pneumothorax. Type 3
collagen is decient in EDS type 4 due to a defect in the
COL3A1 gene. This causes markedly increased fragility of
connective tissues that may lead to uterine rupture in preg-
nancy, intestinal perforation, as well as aortic dilation, dissection, and rupture. EDS-IV affects about 6% of EDS
patients and is the most lethal form of EDS [95].
Shprintzen-Goldberg syndrome (SGS) is another syndrome with a phenotype similar to LDS and MFS, but the
arteriopathy is less severe. SGS phenotypes can include craniosynostosis, arachnodactyly, exophthalmos, hypertelorism,
maxillary and mandibular hypoplasia, low set ears, abdominal hernias, pectus deformity, scoliosis, Chiari I malformations, and aortic dilation. Functionally, these individuals
suffer from developmental delay, mental retardation, and
obstructive sleep apnea. These patients can appear to have a
Marfanoid habitus [96]. This syndrome is typically inherited
in an autosomal dominant pattern, but there must be a causative event that activates the mutation or some germline
mosaicism for the mutation to be expressed. Mutations found
in the SKI gene appear to cause aortic dilation that can lead
to aneurysmal disease. SKI is a SnoN protein that is normally a TGFβ repressor by inhibiting SMAD.SKI competes
with a p300/CBP transcription factor for SMAD binding.
When SKI binds, it converts chromatin into a repressive
state. SKI binds the MH2 domain of the SMAD2/SMAD3
complex, thereby preventing the transcription of TGFβ.
However, when it becomes mutated, there is overexpression
of TGFβ. The upregulation of TGFβ causes increased signaling events, but due to the presence of other repressors of the
TGFβ pathway, the vascular phenotype is less severe than
that of LDS [97].
Turner’s syndrome (TS) occurs in roughly 1in every 2000
live female births. Characterized by short stature, webbed
neck, and premature ovarian failure, these women have normal intelligence. The genotype and phenotype are due to
complete or partial monosomy of the X chromosome. The
most common causes of early fetal demise or later complications are cardiovascular defects. Babies with in utero fetal
demise are typically found to have hypoplastic left heart syndrome. Common cardiovascular manifestations of TS
include bicuspid aortic valves and aortic coarctation [98].
Some develop ascending aortic dilation, dissection, and rupture that are not always associated with bicuspid aortic
valves.
TS is one of the most common causes for aortic dissection
in women. Difculties in diagnosing aortic dilation and predicting rupture may be due in part to the sizing of aortic
diameters in short statured women. Adjustment of aortic
diameter for height or body surface area indicates signicant
aortic dilation in up to 1/3 of women with TS [105]. Twothirds of TS dissections occur in the ascending aorta (see biglycan discussion above).
X-linked Alport syndrome is a familial inherited disorder
of collagen that affects the alpha-5 chain of type 4 collagen.
Type 4 collagen is an important part of basement membranes.
This defect affects the glomeruli of the kidneys leading to
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T. E. Gaines and L. B. Grimsley
renal brosis as well as the cochlea leading to sensorineural
hearing loss. Case reports have identied aortic pathology in
males with X-linked Alport syndrome. Most of the cases
reported involve dissection in young males between the ages
of 20 and 30years. Vascular complications are uncommon in
Alport syndrome but arise due to a lack of appropriate procollagen trimers in the type 4 collagen bers of lamellar
basement membranes in the aortic media. This is caused by
the absence of alpha-5 chains [100].
Cutis laxa, or elastolysis, comprises a group of connective
tissue elastic ber disorders characterized by loose, redundant
skin and may be congenital or acquired. Congenital cutis laxa
syndromes present with variable phenotypes and extracutaneous manifestations including ascending aortic aneurysm, genitourinary and gastrointestinal diverticula, diaphragmatic
hernia, and emphysema that may lead to cor pulmonale and
death in early life. The autosomal dominant form is caused by
a defect in ELN that encodes for elastin and has less severe
involvement of internal organs and vasculature. Autosomal
recessive forms present a more virulent phenotype and are
associated with mutations in FBLN4 and FBLN5. An X-linked
recessive form, now classied with copper deciency syndromes, is caused by a defect in ATP7A [106].
Nonsyndromic FTAADS include a growing number of
conditions with identiable mutations as well as aneurysms
associated with bicuspid aortic valves. The MYH11 gene
and the ACTA2 gene encode for smooth muscle myosin and
actin proteins. Both genes encode muscular elements, and
the mutations have been thought to be associated with upregulation of TGFβ signaling. MYH11 encodes a smooth
muscle myosin heavy chain isoform. The MYH11 gene
mutation is associated with a high penetrance of coexistent
persistent patent ductus arteriosus. ACTA2 encodes for
smooth muscle alpha actin that is also coincidentally
expressed during inammation and is a transcriptional target
of TGFβ signaling [97].
Moyamoya disease is an occlusive vascular disease associated with smooth muscle cell proliferation. This disease
has incomplete penetrance and is more common in persons
of Asian descent. The proliferative arteriopathy in this disease leads to the formation of abnormal collateral vessels in
the brain. These arise to compensate for diminished blood
ow in narrowed internal carotid arteries. These collateral
vessels eventually occlude due to intimal hyperplasia, despite
atrophy of the media layer. There also appear to be defects in
the elastic lamellae of the arteries as well; however, this is
less well characterized [101]. Moyamoya is associated with
FTAADS in individuals with ACTA2 mutations [107].
FTAADs have been primarily found through genome
sequencing in families with a history of aneurysmal disease.
Sequencing reveals deletions and other probable disease
causing mutations, as well as variants of unknown signicance. Variants of unknown signicance are typically found
in coding regions of known genes for brillin, TGFβ pathway constituents, and SM.While current surgical indications
are primarily based on aortic diameter, the association of
specic mutations with phenotypes prone to dissection and
aneurysm formation will allow more effective risk stratication. Some patients will benet from early prophylactic surgery based on their genotype and not size criteria [91].
Bicuspid Aortic Valves
Bicuspid aortic valves (BAV) are the most common congenital cardiac malformation, occurring at a rate of 1–2% [102].
The normal aortic valve consists of three leaets, and bicuspid valves have two leaets often with a raphe fusing adjacent, conjoined leaets. Multiple classication systems exist
based on the number of raphes, the position of the cusps/
raphes, and the functional status of the valve. One such classication system by Sievers and Schmidtke classied bicuspid valves based on the number of raphe. Type 0 has no
raphe, type 1 has one raphe, and type 2 has two raphes. Type
2 bicuspid valves are associated with the highest incidence of
ascending aneurysms according to one study of 304 surgical
patients [103]. The formation of ascending aneurysms in
BAV patients may be caused by the ow dynamics of blood
as it passes through a reduced aortic valve opening. Due to
the position of the cusps, a high velocity jet is continuously
directed toward the convexity of the ascending aorta, eventually causing dilation and dissection or aneurysm [102, 103].
Russo classied bicuspid valves based on where the fusion
of the cusps occurred [104]. Type A valves had fusion of the
left and right coronary cusps. Type B valves had fusion of the
right and noncoronary cusps, and type C valves had fusion of
the left coronary and noncoronary cusps. Russo found that
type A cusps were the most common. Type A cusps affected
a younger subset of patients with a larger mean aortic root
diameter. Based on the histopathology of aortic specimens,
type A valves and their associated aortas had a higher prevalence of brosis, medial necrosis, elastic fragmentation, and
inammation compared to type B valves. This study also
found a direct correlation between the degree of aortic wall
degeneration and the ascending aortic diameter [104].
Patients with bicuspid aortic valves tend to have increased
arterial stiffness due to the degradation of elastin bers
within the aortic wall. There also appears to be abnormal
endothelial cell function with downregulation of endothelial
nitric oxide synthase (eNOS). Due to the downregulation of
eNOS, nitric oxide bioactivity is increased, which subsequently increases MMP2 expression. Increased wall stiffness
in the aorta is thought to be mediated by multiple factors and
cytokines, but specically matrix metalloproteinases like
MMP2. These aortas are then remodeled leading to dilation
of the aortic walls [102].
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Pathology of the Aorta: Inflammatory
https://t.me/med1917
and Noninflammatory Conditions
Predisposing to Aneurysm Formation,
Dissection, and Rupture
Jessica Gulliver and Erin G. Brooks
4
Introduction
The aorta is an elastic artery with a caliber that expands with
systole and recoils during diastole. In adults, it extends an
average of 490cm in length from thoracic initiation to pelvic
bifurcation, and it is anatomically divided into three layers,
i.e. the tunica intima, tunica media, and tunica adventitia
(Fig. 4.1) [1]. The tunica intima is the layer closest to the
aortic lumen and is composed of extracellular matrix proteins
and a few multipotent stromal cells [1, 2]. It includes an endo-
thelial cell layer and extends to the internal elastic lamina
(IEL). The IEL delimits the tunica intima from tunica media
and consists of elastic bers that form a barrier between large
molecules within the circulating blood (e.g. cholesterol) and
the underlying layers of the aortic wall. In newborns, the intimal layer is quite thin with the endothelial cells closely
approximated to the IEL; with “wear-and-tear” aging, intimal
thickness increases due to deposition of extracellular matrix
proteins [3]. The tunica media extends to the external elastic
lamina (EEL) and is the thickest layer of the aorta. Its components are concentrically arranged into lamellar units with
each lamellar unit being composed of a layer of elastic bers
with subjacent smooth muscle cells and some embedded
extracellular matrix including collagen bers and ground substance [1, 2]. In newborns, the number of stacked lamellar
units is only about 35; however, by adulthood, this has generally increased to 50–60 lamellar units [3]. The tunica adventitia is the outermost layer of the aortic wall and is composed
of connective tissue, adipocytes, lymphatic channels, and the
vasa vasorum. Given the width of the aortic wall, a specialized vascular system is needed to supply oxygen and other
nutrients to the parts of the aortic wall furthest from the blood
J. Gulliver (*)
Department of Pathology, University of Wisconsin Hospital
and Clinics, Madison, WI, USA
E. G. Brooks
Pathology and Laboratory Medicine, University of Wisconsin
Hospital and Clinics, Madison, WI, USA
owing within the aortic lumen; thus, the vasa vasorum supplies oxygen and nutrients to the outer third of the tunica
media. Disruption to the normal layers of the aortic wall due
to a variety of diseases can result in signicant morbidity and
mortality. Thus, familiarity with clinicopathologic features
supportive of particular disease processes is advised.
Overview of Aortic Disease
The recent consensus statement on surgical pathology of the
aorta from the Society for Cardiovascular Pathology recommends that aortic diseases detected in surgical pathology
specimens be categorized as either inammatory or noninammatory processes and offers a standardized approach to
the processing of specimens, disease grading, and disease
nomenclature [3, 4]. It is anticipated that such standardization
will result in enhanced understanding of aortic diseases and
improved patient care. Either inammatory or noninammatory aortic disease may ultimately result in serious sequelae
such as aortic aneurysm formation, acute aortic dissection, or
aortic rupture. A brief overview of the pathogenesis and epidemiologic features of aortic aneurysms and aortic dissections is followed by a review of the distinct inammatory and
noninammatory disease processes that may lead to such
phenomena.
Aortic Aneurysm
Pathologically, a true aortic aneurysm is dened as a localized dilatation involving the entire thickness of the wall; it
may be congenital or acquired [5]. A false or pseudoaneurysm, in contrast, is dened as a ruptured arterial wall in
which blood is conned by surrounding tissues forming an
extravascular hematoma [5]. In the United States, true thoracic and abdominal aortic aneurysms represent the 15th
leading cause of death in people greater than age 55 and are
the 19th overall leading cause of death [6].
© Springer Nature Switzerland AG 2019
R. S. Dieter et al. (eds.), Diseases of the Aorta, https://doi.org/10.1007/978-3-030-11322-3_4
45
46
a
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J. Gulliver and E. G. Brooks
b
c
d
e
f
g
Fig. 4.1 (a) Normal layers of the aortic wall with the tunica intima,
tunica media, and tunica adventitia. (b) There is no medial degeneration
present (Alcian Blue/PAS stain). (c) The normal aorta contains elastic
bers in an organized pattern (Elastic stain). (d) Organized elastic bers
without any degenerative changes (Movat’s pentachrome stain). (e)
Medial degeneration within the aortic wall (arrowhead). (f) Elastic ber
fragmentation and loss (arrowheads). (g) Increased extracellular matrix
material (arrowheads)
4 Pathology of the Aorta: Inflammatory and Noninflammatory Conditions Predisposing to Aneurysm Formation, Dissection…
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47
Thoracic Aortic Aneurysm
More than 95% of thoracic aortic aneurysms (TAAs) are
asymptomatic; the prevalence of clinically silent TAAs is
estimated to fall between 0.16% and 0.34% [6]. TAAs are
more common in men compared to women [6, 7]. The
TAA distribution in 60% occur in the root or ascending
aorta, 10% in the arch, 40% in the descending aorta, and
10% in the thoracoabdominal aorta (Fig. 4.2). The incidence of TAAs appears to be increasing [6, 7]. There seems
to be a genetic component to TAAs with 21% of patients
with a TAA having a family member with some sort of
aneurysm. Genetic syndromes such as Marfan syndrome,
Ehlers-Danlos syndrome, Loeys-Dietz syndrome, and
Turner syndrome can have TAAs as part of their clinical
manifestations of the genetic abnormality [6]. Other risk
factors for development of thoracic aortic aneurysm
include aging, systemic hypertension, and bicuspid aortic
valve [7].
Histologically, medial degeneration is commonly seen
in thoracic aortic aneurysm resections. Medial degeneration leads to a weakened aortic wall which predisposes to
dilatation and eventual aneurysm formation. Mucoid extracellular matrix accumulation, loss of smooth muscle cells
with disarray, elastic ber degeneration, and disorderly
arrangement are some features of medial degeneration [3,
7]. In patients with Marfan syndrome, mutations in bril-
lin-1 are found. Fibrillin-1 is important to the construction
of microbrils in the extracellular matrix. Medial degeneration is often signicant in patients with Marfan syndrome [7].
Fig. 4.2 Thoracic Aortic Aneurysm Rupture with hemorrhage (arrow
demonstrating aortic arch rupture). Brachiocephalic Artery, Left
Common Carotid Artery, and Left Subclavian Artery are adjacent to
area of rupture
Abdominal Aortic Aneurysm
Abdominal aortic aneurysms (AAAs) are more common in
occurrence when compared to TAAs; up to 80% of aortic
aneurysms occur below the renal arteries [7]. Most are due to
atherosclerosis, but other causes such as inammatory aneurysm, tuberculous aneurysm, medial degeneration, or infectious aneurysm are possible [7]. Risk factors for AAAs
include smoking, increasing age, greater height, coronary
artery disease, atherosclerosis, hypercholesterolemia, and
hypertension [7, 8]. Like thoracic aortic aneurysms, genetics
also can play a role in AAAs with 12–19% of those patients
having an abdominal aneurysm repair being related to a rst
degree relative with an AAA [8]. In addition, patients with
Ehlers-Danlos type IV who have a defect in their type III
collagen synthesis are at an increased risk of AAA [8].
Atherosclerotic plaques play a role in development of
AAAs. Signicant inammatory inltrates including numerous macrophages and lymphocytes are common in AAAs
which may contribute to extracellular matrix degeneration.
Histologically, elastic ber loss, medial smooth muscle cell
degeneration, and brosis can be seen. Another common
nding is thrombus formation within the aortic lumen associated with the aneurysm. Enzymes such as collagenase and
elastase may be upregulated contributing to aneurysmal dilatation [7].
Aortic Dissection
Approximately 3/100, 000 persons/year develop an aortic dissection with a slight male predominance. Risk factors for an
aortic dissection include age, inherited genetic connective tissue diseases such as Marfan syndrome and Ehlers-Danlos syndrome, hypertension, aortic valvular disease such as bicuspid
aortic valve, trauma, prior aortic operations, and cocaine
abuse. The most common symptoms are back, abdominal, or
chest pain [9]. An aortic dissection occurs when a tear develops in the intimal layer allowing blood to enter into the tunica
media layer creating a true lumen and a false lumen (Figs.4.3,
4.4, and 4.5). In cases related to an intimal tear, 60% occur in
the ascending aorta, 25% in the descending aorta, and 10% in
the arch and abdominal aorta [9]. Other causes of aortic dissection could be bleeding from the vasa vasorum in the tunica
adventitia into a weakened tunica media layer.
Aortic dissections are often classied into two types:
Stanford Type A which occurs in the ascending aorta and
Stanford Type B which originates in the descending aorta
[9]. Approximately 60% of patients develop Type A dissections with the incidence peaking between 50–60years of age
[9]. In patients with inherited connective tissue diseases, a
common histological nding is medial degeneration which is
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