Cardiovascular Pathology


Pathogenesis of Atherosclerosis



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Pathogenesis of Atherosclerosis



  • Postulate: Atherosclerosis is an inflammatory disease, and advanced lesions in the arteries are similar to end-stage inflammatory changes in other tissues (e.g. cirrhosis in liver, glomerulosclerosis in kidney)





Notes:

Chlamydia pneumoniae has been demonstrated in plaques. Antibiotics against C. pneumoniae have reduced recurrent events in patients with ischemic heart disease.

Certain viruses cause atherosclerotic plaques in chickens.

Some areas of endothelium may generate more superoxide dismutase, accounting in part for the nonrandom localization of atherosclerosis.


Medial smooth muscle may have a heterogeneous embryologic origin & may respond differently, accounting in part for the nonrandom localization of atherosclerosis.

“Inflammatory lesion” is an oversimplification. AS is perhaps better described as an ongoing process of injury and imperfect repair.


Could plaques be benign neoplasia or caused by an oncogenic virus? Unlikely – some plaques probably are monoclonal, but probably just arise from pre-existing developmental clones.


There is evidence that the fine particulate matter (soot) in diesel exhaust may act synergistically with cholesterol to activate genes that cause inflammation of blood vessels (Genome Biology 2007, 8:R149).

Aneurysm



  • Def: An abnormal dilatation or outpouching of a blood vessel, usually the aorta (or even the heart!)

  • True: Has all layers of vessel wall (c.f. true diverticulum in bowel)

  • False: Not all layers (pseudoaneurysm – c.f. false diverticulum in bowel)

  • Most common causes: Atherosclerosis and cystic medial degeneration

Notes:

An extravascular hematoma or dissection of blood into the media of a vessel are examples of false aneurysms.



Other Causes of Aneurysms




  • Syphilis (typical in thoracic aorta/arch)

  • Infections (“mycotic”)

  • Congenital defects

  • Trauma

  • Vasculitis (Kawasaki disease, polyarteritis nodosa)

Notes:

“Mycotic” refers to any infection, bacterial or fungal. Can be true of false.


See Appendix II for Kawasaki pearls.

Abdominal Aortic Aneurysms

  • Occur most commonly from below the renal arteries to the bifurcation, & may extend into the iliacs

  • Are “true”


  • Are due to weakening and thinning of the media by atherosclerosis

  • Occurs >50 yo, M>F

  • There is a genetic predisposition, possibly related to a weaker media

  • Can be saccular, fusiform, cylindroid, serpiginous

  • Can contain abundant mural thrombus

  • Can obstruct ostia of renals, SMA, IMA, vertebrals

  • Variants are inflammatory and mycotic

Notes:

AAA’s are usually not initiated by a primary abnormality of the media (although a weaker media may predispose). The media is secondarily weakened by severe atherosclerotic involvement of the intima.

Inflammatory AAA’s feature dense periaortic fibrosis and lymphoplasmacytic inflammation. The cause may be a recently recognized entity, “immunoglobulin G4 (IgG4)-related disease.” This fibrosing, autoimmune disorder can also affect the pancreas, salivary glands and biliary system. It responds to steroid therapy.

A typical AAA can become secondarily infected (mycotic) esp. from Salmonella gastroenteritis – this may lead to rapid dilatation and rupture.



AAA Rupture




  • The dreaded complication

  • 4 cm is the “cutoff” for risk of surgery less than risk of rupture (varies a little among institutions)

  • Newer stent devices now available – can be placed via intravascular route

Note:

At 4 cm, about 5 – 10% per year rupture.




Other AAA Complications




  • Occlusion of a branch

  • Embolization of thrombus or atheromatous material

  • Compression of a ureter

  • Compression/erosion of a vertebral body causing back pain




Syphilitic (Luetic) Aneurysms




  • A complication of tertiary syphilis – not common now

  • Is due to obliterative endarteritis which weakens the media

  • Is more typical in the thoracic aorta (not abdominal)

  • May cause very irregular intimal scarring (tree barking)

  • Accelerates atherosclerosis of root and arch

Note:

Syphilitic thoracic aortic aneurysms may cause dramatic dilation of the aorta with protrusion of the aneurysm through the thoracic inlet into the neck!




Complications of Syphilitic (Luetic) Aneurysms




  • May extend to the aortic valve ring and cause dilatation and valvular insufficiency, leading to volume overload hypertrophy of heart, sometimes massive – cor bovinum

  • Most pts with syphilitic AA die of heart failure secondary to AV incompetence



Aortic Dissection




  • AKA dissecting hematoma

  • Old term “dissecting aortic aneurysm”

  • Occurs in two clinical settings:

    • Middle aged men with hypertension

    • Connective tissue disorders like Marfan’s (usually younger)

  • Usually not seen with severe atherosclerosis (the extensive scarring of AS may be protective)

  • May occur rarely in pregnancy, or even without an obvious cause



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