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Flashcards in Aneurysm Deck (11)

Types of aneurysm

True aneurysms involve all layers of the blood vessel, intima, media, and externa

Saccular: on just one side

Fusiform: bulged out everywhere in s circle

Pseudoaneurysm: break in the intima/media, and a hematoma forms forming a bulged sac in the connective tissue externa.


What are the two types of aortic aneurysms?

What are the age groups, prevalence, and main risk factors of each?

Abdominal aortic aneurysms,
~5% prevalence in aged over 65 years. More in men.

Atherosclerosis is the main risk factor.

Thoracic aortic aneurysm,
Are rare and can occur at any age

Main risk factor is inherited connective tissue disorders


Ehlers-Danlos syndromes

What genetic defects cause them?

What are the 6 major points where defects can cause the disease?

Defects of collagen synthesis or cross-linking

Can be autosomal dominant or recessive and can result from many different mutations. 3 most common: Lysyl hydroxylase deficiency, Deficient collagen 3 synthesis, Deficient Collagen 5

1) Transcription

2) Translation, ER hydrophobic localization signal, hydrophobic portion cleavage.

3) Post-translational modifications

4) Hydroxylation of prolines and lysines, and glycosylation of those hydroxylysines, -lysyl hydroxylase defect.

5) C and N terminal propeptide cleavage, needed to form tropocollagen

6) Cross linking of tropocollagens into collagen strands, by lysyl-oxidase.


Ehlers-Danlos syndromes


Hyper-extensible skin
Hyper-mobile joints

Skin is fragile and vulnerable

eye fragility, retinal detachment and cornea ruptures.

Diaphragmatic hernias

Increased colon ruptures

Increased vessel ruptures, aneurysms, dissections.


What causes Marfan Syndrome.

What are the major tissues affected.

Mutations to the fibrillin-1 gene. Many different specific mutations cause it, but all to this gene.

FIBRILLIN is a main component of extracellular matrix MICROFIBRILS

Fibrillin is a scaffolding protein for tropoelastin which anchors elastic fibers.

Thus tissues with lots of elastin are dysfunctional. --> large vessels, ligaments, and ciliary fibers of the eye lens.

The ECM is also a major site of storage/sequestration for TGF-beta. and pathology may also be caused by excessive TGF-beta signaling in Marfan patients.


Marfan Syndrome symptoms

Skeletal abnormalities, with excessively long and slender bones, arms, legs, fingers, etc.

Bilateral subluxation, sinking of the lens of the eye, due to the weak ciliary fibers. This is essentially diagnositc for Marfam syn because it almost never happens otherwise.

Hyperflexibility and hyperextensibility of joints.

Spinal deformities

Chest deformities, Pigeon breasted or "pectus excavatum" sunken chest/sternum.

Most serious symptom is the propensity for aortic aneurysms, dissections, and ruptures. Most common marfan cause of death.

Floppy valve syndrome is also common, due to weak valves. Mitral regurgitation, which eventually leads to heart failure.


Loeys-Dietz syndrome is caused by

Autosomal dominant mutations to the TGF-beta receptors, ligands, or SMAD3

TGF-beta receptors 1 or 2
TGFB1 or TGFB2 ligands

or to SMAD-3 of the TGF-beta intracellular signaling pathway.


Loeys-Dietz syndrome symptoms

Enlarged, tortuous aorta is the main symptom.

Arterial tortuosity is also present in the rest of the vasc. system.
Weakened connective tissue.
Aneurysms, dissections, ruptures.

Heart malformations, septal defects, patent ductus arteriosus,

Skeletal malformations.
Skull bones fuse prematurely, facial deformity, wide spaced eyes, cleft palate.

Sunken or protruded chest like marfans.

Flat or clubbed feet.
Hand and finger malformations.


What causes Arterial Tortuosity Syndrome?

Autosomal recessive defects to the gene coding for GLUT10 transporter.

It is somehow involved in regulation of the TGF-beta signaling pathway.

May also regulate the cellular uptake of dehydroascorbic acid (DAA),
which then activates prolyl-hydroxylase, needed for tropocollagen synthesis and secretion.

BUT the main physical thing is dysregulated elastic fibers and decreased numbers of elastin sheets around the vessels.


Arterial tortuosity syndrome symptoms

decreased elastin lamellae in the arterial walls

arterial walls are less compact and weaker

long, tortuous vessels and arota

facial dysmorphia

Hyper extensible joins


ECM TGF-beta binding proteins that are disrupted in marfan synderom

No fibrillin-1 gene, no microfibrils,

No LTBP: Latent TGF-beta Biding Protein

No LLC: Large Latent Complex.
TGF-beta in complex with LTBP.