Aneurysm and Dissection

Based on Robbins & Kumar Basic Pathology and Robbins, Cotran & Kumar Pathologic Basis of Disease

Overview and Definitions

Fig. 11.16 from Robbins Cotran: A = Healthy vessel, B = True aneurysm (saccular), C = True aneurysm (fusiform), D = False aneurysm (pseudoaneurysm), E = Dissection

TYPES OF ANEURYSMS

1. True Aneurysm

• Atherosclerotic aneurysms
• Congenital vascular aneurysms
• Ventricular aneurysms following transmural MI

2. False Aneurysm (Pseudoaneurysm)

• Ventricular rupture after MI contained by a pericardial adhesion
• Leak at a vascular graft-artery anastomosis

3. By Morphological Shape

PATHOGENESIS OF ANEURYSMS

Fig. 11.17: A = Healthy aortic wall; B = Atherosclerotic damage with laminar medial collapse; C = Inflammatory vasculitis with immune cell infiltration; D = TGF-β signaling pathway (mutated genes marked with asterisks)

The Two Most Important Causes:

• Atherosclerosis - greater factor in abdominal aortic aneurysms (AAA)
• Hypertension - most common etiology in ascending aortic aneurysms

Specific Mechanisms of Wall Weakening:

• Ehlers-Danlos syndrome (vascular type): Defective type III collagen synthesis creates inherently weak vessel walls.

• Marfan Syndrome: Mutation in fibrillin-1 gene. Fibrillin-1 normally sequesters TGF-β bound to ECM. Without fibrillin, TGF-β is released excessively, driving MMP transcription and disrupting ECM. Primarily affects the ascending aorta.
• Loeys-Dietz Syndrome: Mutations in TGF-β receptors (TGFBR1/2), SMAD3, or TGF-β3 itself cause overactive TGF-β signaling. Aneurysms can rupture at small sizes.

• Atherosclerotic thickening of the intima increases the diffusion distance for O₂ and nutrients to reach medial SMCs → inner medial ischemia → SMC loss.
• Hypertension narrows arterioles of the vasa vasorum → outer medial ischemia.
• Syphilis (tertiary): Obliterative endarteritis of vasa vasorum of the thoracic aorta → medial ischemia → SMC loss, elastic fiber loss → inadequate ECM synthesis.

MICROSCOPIC FEATURES (Medial Degeneration)

• Loss and fragmentation of elastic fibers in the tunica media
• Loss of smooth muscle cells (SMCs) - laminar medial collapse
• Accumulation of proteoglycans/mucoid material in the spaces vacated by SMCs and elastic tissue (gives a "cystic" appearance)
• Fibrosis of the media
• In atherosclerotic AAA: severe complicated atherosclerotic changes with destruction and thinning of the underlying aortic media
• In inflammatory AAA: adventitial and periaortic lymphoplasmacytic infiltrate (may suggest IgG4-related disease)
• Mural thrombus formation in the lumen of the aneurysm

1. ABDOMINAL AORTIC ANEURYSM (AAA)

Pathogenesis

• Atherosclerosis is the primary cause - destroys and thins the underlying aortic media
• Smoking is a major independent risk factor
• Other contributors: aging, male sex, genetic predisposition (MMP/TIMP polymorphisms), inflammatory mediators (Th2 cytokines shifting macrophages toward elastolytic MMP production)
• Rarely develops before age 50; occurs more frequently in males and smokers

Microscopic Features (Morphology)

• Located between the renal arteries and the aortic bifurcation
• Severe complicated atherosclerosis with destruction and thinning of the underlying aortic media
• Frequently contains bland, poorly organized mural thrombus
• Size: >3 cm, often >5.5 cm in diameter; up to 25 cm in length
• Can be saccular or fusiform

Clinical Features

• Most AAAs are asymptomatic for years - discovered incidentally on imaging
• Rupture is the most feared complication - presents as sudden-onset severe abdominal/back pain with hypotension (surgical emergency with high mortality)
• Pulsatile abdominal mass - palpable in thin patients
• Compression of adjacent structures can cause ureteral obstruction, venous compression
• Atheroembolism - thrombus/atherosclerotic debris can embolize to distal vessels (legs)
• Thrombosis of the aneurysm with occlusion
• Risk of rupture correlates with size: >5.5 cm warrants surgical repair

2. THORACIC AORTIC ANEURYSM (TAA)

Pathogenesis

• Hypertension is the most common cause of ascending aortic aneurysms
• Marfan syndrome / Loeys-Dietz syndrome - TGF-β signaling dysregulation (see above)
• Tertiary syphilis - classically causes ascending thoracic aneurysms via obliterative endarteritis of the vasa vasorum
• Aortitis (e.g., giant cell arteritis, Takayasu arteritis)
• The ascending thoracic aorta is particularly vulnerable to medial degeneration because it bears the highest pulsatile hemodynamic stress

Microscopic Features

• Same underlying medial degeneration:
  • Loss of elastic laminae
  • SMC drop-out / laminar medial collapse
  • Mucoid/proteoglycan accumulation in the media
• In syphilitic aortitis: obliterative endarteritis of vasa vasorum → adventitial/medial lymphoplasmacytic infiltration → elastic fiber destruction
• In Marfan syndrome: the medial changes are diffuse with the above features

Clinical Features

• Can cause aortic root dilation → aortic valve incompetence/regurgitation (wide pulse pressure, diastolic murmur)
• Compression of mediastinal structures:
  • Trachea/bronchi → cough, dyspnea, stridor
  • Esophagus → dysphagia
  • Recurrent laryngeal nerve → hoarseness
  • Superior vena cava → SVC syndrome (facial plethora, arm swelling)
• Chest/back pain - deep, boring pain
• Syphilitic aneurysms typically involve the ascending aorta and arch - can produce a "tree-bark" appearance of the intima (wrinkled, pearly-white)
• Rupture into the pleural space or pericardium

3. AORTIC DISSECTION (Thoracic and Abdominal)

Definition

Pathogenesis

• A tear in the intima (most common) allowing blood to track between the media layers
• OR rupture of the vasa vasorum within the media, causing a medial hematoma that then dissects the layers

• Hypertension (most common systemic risk factor) - present in >90% of cases; causes ischemia of inner media via intimal thickening and ischemia of outer media via vasa vasorum damage
• Marfan syndrome / Loeys-Dietz syndrome - fibrillin/TGF-β pathway defects
• Iatrogenic - cardiac catheterization, intra-aortic balloon pump insertion
• Pregnancy - increased hemodynamic stress (especially in 3rd trimester)
• Bicuspid aortic valve - associated with underlying medial degeneration
• Cocaine use - severe hypertensive surges

• Type I: Originates in ascending, extends to arch and beyond
• Type II: Confined to ascending aorta
• Type III: Originates in descending thoracic aorta

Microscopic Features

• Medial degeneration is the histological precondition: loss of elastic laminae, SMC dropout, mucoid change
• The dissection plane runs through the outer media or at the media-adventitia junction - this is the plane of cleavage
• Separation of the elastic lamellar units by blood - creating a false lumen
• No true inflammatory reaction in the acute phase
• The false lumen may contain organized thrombus in older dissections
• The intimal tear is typically a transverse laceration (5-6 cm above the aortic valve in Type A)

Clinical Features

• Classic presentation: Sudden onset of severe, tearing or ripping chest pain that radiates to the back/interscapular region - described as the "worst pain of my life"
• Pain may migrate distally as the dissection propagates
• Hypertension is typically present at presentation
• Pulse deficits: unequal blood pressure in arms (>20 mmHg difference); weak or absent pulses in branches of the aorta as they are compromised
• Aortic regurgitation (Type A) - diastolic murmur, wide pulse pressure - due to aortic root involvement
• Neurological signs - stroke, paraplegia (spinal cord ischemia from intercostal/spinal artery compromise)
• Cardiac tamponade - if dissection extends retrograde into the pericardium (Type A) → Beck's triad (hypotension, muffled heart sounds, raised JVP)
• MI - if dissection involves coronary ostia (right coronary more often)
• Chest X-ray findings: widened mediastinum, pleural effusion (hemothorax)

• Less common than thoracic; usually an extension of a Type B dissection
• Abdominal/back pain - severe, tearing character
• Mesenteric ischemia if superior mesenteric artery or celiac trunk orifices are compromised → abdominal pain, bloody diarrhea
• Renal ischemia - if renal arteries are involved → oliguria, acute kidney injury, new-onset hypertension
• Lower limb ischemia - if iliac arteries compromised → pulseless, cold legs
• Without treatment: death from external rupture (hemorrhage into pleural cavity, peritoneum, or mediastinum)

4. ARTERIAL DISSECTION (General Concept)

• Blood entering a defect in the vessel wall
• Tunneling through medial or medial-adventitial planes
• Creating a false lumen alongside the true lumen

• ~80% mortality within 2 weeks for untreated Type A dissection
• Rupture through the adventitia causes massive hemorrhage

Summary Table