Pathology of Blood Vessels 1

What are the common clinical manifestation of aortic dissection (6)?

-Cardiac tamponade -Aortic insufficiency -Retrograde dissection into the aortic root causes disruption of the aortic valve -Extension into the coronary arteries results in AMI -Extension into the great arteries of the neck or renal, mesenteric, or iliac arteries causes critical vascular obstruction and ischemia -Compression of spinal arteries may cause transverse myelitis

How are vasculitides classified by etiology (4)?

-Immune complex mediated vasculitis -Infectious vasculitis -Noninfectious vasculitis -Physical and chemical injury

Which patients are more likely to develop an abdominal aortic aneurysm (3)?

-More frequent in men and in smokers -Rarely develops before age 50 -Other factors must contribute since the incidence is is less than 5% in men older than 60 years of age despite almost universal abdominal aortic atherosclerosis in that population

What is the etiology of an inflammatory abdominal aortic aneurysm?

Uncertain.

What causes fibromuscular dysplasia?

Unknown cause, probably developmental; first-degree relatives of affected individuals have an increased incidence.

What is noninfectious vasculitis?

Vasculitis caused by immune complexes generated by infection or cross-reactivity.

What is cystic medial degeneration?

"Degenerative changes" due to any etiology are collectively called cystic medial degeneration which is nonspecific and can be seen in a variety of settings, including Marfan syndrome and scurvy.

Describe the appearance of hyperplastic arteriolosclerosis.

"Onion-skin lesions" with concentric, laminated thickening of the vessel walls leading to luminal narrowing.

Give the risk of rupture associated to abdominal aortic aneurysm size (4).

- < 4 cm: close to 0% -4-5 cm: 1% per year -5-6 cm: 11% per year - > 6 cm: 25% per year

What are the contributing factors in the development of aortic aneurysms (5)?

-Atherosclerosis -Hypertension -Trauma -Vasculitis -Infections

What are some examples of true aneurysms (4)?

-Atherosclerotic -Syphilitic -Congenital vascular aneurysms -Ventricular aneurysms that follow transmural myocardial infarctions

Describe how atherosclerosis contributes to the development of an abdominal aortic aneurysm (3).

-Atherosclerotic plaque in the intima compresses the underlying media and compromises nutrient and waste diffusion from the vascular lumen into the arterial wall -Media undergoes degeneration and necrosis resulting in arterial wall weakness and consequent thinning -The major cause of aneurysm formation is the production of MMPS by inflammatory cells

Describe the pathogenesis of ischemia (3).

-Atherosclerotic thickening of the intima increases the distance that oxygen and nutrients must diffuse -Systemic hypertension causes narrowing of vasa vasorum (e.g., in the aorta) and leads to outer medial ischemia -Smooth muscle cell loss or change in synthetic phenotype

Describe Monckeberg medial sclerosis (4).

-Characterized by calcific deposits in muscular arteries in persons typically older than age 50 -Deposits may undergo metaplastic change into bone -Lesions do not narrow the vessel lumen -Usually not clinically significant

What is the etiology of a mycotic abdominal aortic aneurysm (2)?

-Circulating microorganisms lodge in the aortic wall and cause inflammation -Bacteremia from a primary Salmonella gastroenteritis is a common cause

What are the causes of arteriovenous fistulas

-Congenital areteriovenous malformation - AVM - most common -Rupture of an arterial aneurysm into an adjacent vein -Penetrating injuries that pierce arteries and veins -Inflammatory necrosis of adjacent vessels -Iatrogenic, created to provide vascular access for chronic hemodialysis

List the congenital abnormalities of the vessels (3).

-Congenital weakness of the vessel walls -Arteriovenous fistulas -Fibromuscular dysplasia

Give a brief description of Marfan syndrome and how it contributes to the aneurysm formation.

-Defective synthesis of the scaffolding protein fibrillin leads to aberrant TGF-β activity and progressive weakening of elastic tissue -Progressive dilation of aorta due to remodeling of the poor quality of the elastin in the media

How is inflammation involved in the pathogenesis of aneurysms (4)?

-Destructive proteolytic enzymes are produced by inflammatory cells -Macrophages produce MMPs in atherosclerotic plaque or in vasculitis -MMPs degrade components of the ECM in the arterial wall (collagens, elastin, proteoglycans, laminin, fibronectin) -Decreased release of tissue inhibitor of metalloproteinase (TIMP) expression contributes to the overall ECM degradation

How does an abdominal aortic aneurysm affect the renal and superior or inferior mesenteric arteries (2)?

-Direct pressure -Narrowing or occlusion of vascular ostia by mural thrombi

What are the signs and symptoms of a thoracic aortic aneurysm (9)?

-Encroachment on mediastinal structures -Respiratory difficulties due to encroachment on the lungs and airways -Difficulty in swallowing due to compression of the esophagus -Persistent cough due to irritation of or pressure on the recurrent laryngeal nerves -Pain caused by erosion of bone (i.e., ribs and vertebral bodies) -Aortic valve dilation with valvular insufficiency -Narrowing of the coronary ostia causing myocardial ischemia -Rupture -Most patients with syphilitic aneurysms die of heart failure due to aortic valve incompetence

Describe the healing stage of vascular response to injury (4).

-Endothelial cells migrating from adjacent uninjured areas and circulating precursors originating in bone marrow fill areas of denudation -Medial smooth muscle cells or smooth muscle precursor cells migrate into the intima, proliferate, and synthesize ECM (analogous to fibroblasts filling in a wound) -Results in the formation of a neointima -Healing results in permanent intimal thickening

What are the constitutional signs of vasculitis (4)?

-Fever -Malaise -Myalgias -Arthralgias

Describe the process of vasculogenesis (3).

-Hemangioblast angiogenic precursors migrate to the sites of vascularization and differentiate into endothelial cells -Primary growth factors involved: isoforms of vascular endothelial growth factor (VEGF) -Stabilization of newly formed tubes requires recruitment of pericytes and smooth muscle cells; angiopoietin 1 binding to endothelial cell Tie2 receptors is required

What are the anatomic variants of arteriolosclerosis (2)?

-Hyaline -Hyperplastic

Compare the causes of hyaline arteriolosclerosis versus hyperplastic arteriolosclerosis.

-Hyaline arteriolosclerosis results from plasma protein leakage into the vascular wall -Hyperplastic arteriolosclerosis results proliferation of intimal smooth muscle and reduplication of basement membranes

Which pathologic processes fall under the category of malignant hypertension (2).

-Hyperplastic arteriolosclerosis -Fibrinoid necrosis in the renal arteriolar wall

List the factors that cause aneurysms due to altered balance of collagen degradation and synthesis (2).

-Inflammation -Genetic predisposition

What are the stages of vascular response to injury (3)?

-Intimal thickening -Endothelial cell loss or dysfunction -Healing

What are the consequences associated with arteriovenous fistulas?

-Large fistulas become clinically significant by shunting blood from the arterial to the venous circulations and may result in high-output cardiac failure -An important cause of intracerebral hemorrhage

List the disorders that cause aneurysms due to poor intrinsic quality of the vascular wall connective tissue (4).

-Marfan syndrome -Loeys-Dietz syndrome -Ehlers Danlos syndrome -Vitamin C deficiency

What is the etiology of thoracic aortic aneurysms (4)?

-Most commonly associated with hypertension -Marfan syndrome -Loeys-Dietz syndromes -Syphilis (historically)

Give a brief description of Loeys-Dietz syndrome and how it contributes to aneurysm formation.

-Mutations in TGF-β receptors lead to abnormalities in elastin and collagen I and III -Even small aneurysms can rupture easily

Which infections are associated with the development of aortic aneurysms (4)?

-Mycotic aneurysms due to a septic embolus -Extension of an adjacent suppurative process -Circulating organisms can directly infect the arterial wall -Tertiary syphilis

Give the two mechanisms through which vascular pathology results in disease.

-Narrowing (stenosis) or complete obstruction of vessel lumens, either progressively (e.g., by atherosclerosis) or precipitously (e.g., by thrombosis or embolism) -Weakening of vessel walls, leading to dilation or rupture

Describe the pathological process of an aortic aneurysm due to a tertiary syphilis (4).

-Now a rare cause of aortic aneurysms -The obliterative endarteritis characteristic of late-stage syphilis has a predilection for small vessels, including vasa vasorum of the thoracic aorta -Ischemic injury of the aortic media leads to weakening and aneurysmal dilation, which sometimes involves the aortic valve annulus

List the types of patients who experience arterial dissection (4).

-Occurs most of often in hypertensive men, aged 40 to 60 years (>90% of cases) -Younger patients have systemic or localized abnormalities of connective tissue affecting the aorta (e.g., Marfan syndrome) -Iatrogenic (e.g., complicating arterial cannulations during diagnostic catheterization or cardiopulmonary bypass) -During or after pregnancy

What are the causes and complications of arterial dissection?

-Often aneurysmal but not always -May rupture

What are some examples of false aneurysms (2)?

-Post-MI ventricular rupture that is contained by a pericardial adhesions -Leak at the sutured junction of a vascular graft with a natural artery

What are the clinical consequences of having an abdominal aortic aneurysm (5)?

-Presents as a pulsatile abdominal mass that simulates a tumor -Rupture into the peritoneal cavity or retroperitoneal tissues with massive, potentially fatal hemorrhage -Obstruction of a branch vessel resulting in ischemic injury of downstream tissues, e.g. iliac (leg), renal (kidney), mesenteric (gastrointestinal tract), or vertebral (spinal cord) arteries -Emboli from atheroma or mural thrombus -Impingement on an adjacent structure, e.g., compression of a ureter or erosion of vertebrae

Which vessels is fibromuscular dysplasia most common in (4)?

-Renal (renovascular hypertension) -Carotid -Splanchnic -Vertebral

What are the features of the synthetic phenotype of ischemia (4)?

-Scarring -Loss of elastic fibers -Inadequate ECM synthesis -Production of increased amounts of amorphous ground substance (glycosaminoglycans)

What pathologic processes of hyperplastic ateriolosclerosis contribute to the luminal narrowing (2)?

-Smooth muscle cell proliferation -Thickened, reduplicated basement membranes

What are the classical clinical symptoms of aortic dissection (3)?

-Sudden onset of excruciating pain, usually beginning in the anterior chest, radiating to the back between the scapulae -Pain moves downward as the dissection progresses -Symptoms can be confused with myocardial infarction

What are the clinical outcomes of aortic dissection (3)?

-Used to be fatal, but now 65-75% of patients survive due to rapid diagnosis, intensive anti-hypertensive therapy, and surgery involving plication of the aortic wall -The most common cause of death is rupture of the dissection outward into the pericardial, pleural, or peritoneal cavities

Describe the morphology of an abdominal aortic aneurysm (6).

-Usually below the renal arteries and above the bifurcation of the common iliac arteries -Saccular or fusiform, up to 15 cm in diameter, and up to 25 cm in length -Intimal surface typically shows severe complicated atherosclerosis with destruction and thinning of the underlying aortic media -Frequently contains a laminated, poorly organized mural thrombus, which may partially or completely fill the dilated segment -Renal and superior or inferior mesenteric arteries may be affected -Often accompanied by smaller aneurysms of the iliac arteries

How can vasculitides be classified (6)?

-Vessel size -Immune complexes -Specific autoantibodies -Granuloma formation -Specific organ -Population demographics

What are the characteristics of inflammatory aortic aneurysms?

Characterized by dense periaortic fibrosis and abundant lymphoplasmacytic inflammation with many macrophages and often giant cells.

What is vasculogenesis?

De novo formation of blood vessels during embryogenesis.

Give a brief description of Ehlers Danlos syndrome.

Defective type III collagen synthesis.

What are fusiform aneurysms?

Diffuse, circumferential dilation of a long vascular segment They vary in diameter (up to 20 cm) and in length and may involve extensive portions of the aortic arch, abdominal aorta, or iliac arteries.

What is infectious vasculitis?

Direct invasion of vascular walls by pathogens.

Is arterial dissection common is patients with syphilis?

Dissection is unusual in the presence of substantial medial scarring such as syphilis, presumably because the medial fibrosis inhibits propagation of the dissecting hematoma.

How can hyperplastic arteriolosclerosis damage the kidney in particular?

Fibrinoid deposits and vessel wall necrosis (necrotizing arteriolitis) in extreme cases are seen particularly in the kidney.

What is fibromuscular dysplasia?

Focal irregular thickening of the walls of medium and large muscular arteries.

What is the end result of fibromuscular dysplasia?

Luminal stenosis.

How much do abdominal aortic aneurysms grow per year?

Most aneurysms expand at a rate of 0.2 to 0.3 cm/yr, but 20% expand more rapidly.

What is angiogenesis?

New vessel formation in the mature organism.

When does hyperplastic arteriolosclerosis present?

Occurs in severe (malignant) hypertension of a blood pressure greater than 240/120 mmHg.

What is the mortality of abdominal aortic aneurysms?

Operative mortality for unruptured AAAs is approximately 5%; emergency surgery after rupture has a mortality rate of > 50%.

What causes hyaline arteriolosclerosis?

Plasma protein leakage across injured endothelial cells and increased smooth muscle ACM in response to chronic hemodynamic stress.

Which type of aortic dissections are most dangerous?

Proximal dissections.

What is arteriogenesis?

Remodeling of existing arteries in response to chronic changes in pressure or flow. It results from an interplay of endothelial cell and smooth muscle cell derived factors.

What aspect of an abdominal aortic aneurysm is related to its risk of rupture?

Size.

What type of vessels are most commonly affected by vasculitis?

Small vessels, from arterioles to capillaries to venules. Several of the vasculitides tend to affect only vessels of a particular size or particular vessel beds.

What are arteriovenous fistulas?

Small, direct connections between arteries and veins.

What are saccular aneurysms?

Spherical outpouchings involving only a portion of the vessel wall. They vary from 5 to 20 cm in diameter and often contain thrombus.

How does a mycotic abdominal aortic aneurysm lead to dilation and rupture of the aorta?

Suppuration destroys the media.

What determines the clinical features of the different forms of vasculitis?

The vascular bed affected (e.g., central nervous system vs. heart vs. small bowel).

What is the consequence of having a congenital weakness of the vessel walls?

They lead to berry aneurysms in cerebral vessels (particularly in the circle of Willis at the base of brain), which may rupture and cause fatal intracerebral hemorrhage.

In addition to hypertension, in which other patients is hyaline arteiolosclerosis seen (3)?

Vessels of normo- or hypertensive elderly persons also frequently show hyaline arteriosclerosis, but in hypertension it is more generalized and severe -In nephrosclerosis due to chronic hypertension the arteriolar narrowing of hyaline arteriosclerosis causes diffuse impairment of renal blood supply and glomerular scarring -Diabetic microangiopathy has similar lesions

The presence of abdominal aortic aneurysm is indicative of what other conditions?

A person with AAA is very likely to have atherosclerosis in other vessels and has an increased risk of IHD and stroke.

How does endothelial cell loss or dysfunction lead to the thickening of the intima?

It stimulates smooth muscle cell growth and ECM synthesis causing thickening of the intima.

What is a false aneurysm?

A defect in the vascular wall which leads to an extravascular hematoma that freely communicates with the intravascular space ("pulsating hematoma") .

What is an aneurysm?

A localized congenital or acquired abnormal dilation of a blood vessel or the heart. Rupture has catastrophic consequences.

How are aneurysms greater than 5cm managed?

Aggressively, usually by surgical bypass involving prosthetic grafts. Endoluminal stent grafts (expandable wire frames covered by a cloth sleeve) are used in selected patients.

Give a brief description of vitamin C deficiency.

Altered collagen cross-linking.

Fibromuscular dysplasia is most commonly seen in which patients?

It is most frequently found in young women.

What is a complication of the development of fibromuscular dysplasia?

Aneurysms may develop in adjacent vessel segments with attenuated media leading to rupture.

What is the most common condition associated with the development of an abdominal aortic aneurysm?

Atherosclerosis.

What is the most common etiology of an abdominal aortic aneurysm?

Atherosclerosis.

What is the most frequent and clinically important pattern of arteriosclerosis?

Atherosclerosis.

What is an arterial dissection?

Blood enters the arterial wall itself as a hematoma dissecting between its layers.

What is vasculitis?

General term for vessel wall inflammation. There are more than 20 forms identified.

What is arteriosclerosis?

Generic term reflecting arterial wall thickening and loss of elasticity; hardening of the arteries.

What are the genetic predispositions that contribute to aneurysm formation?

Genetic polymorphisms of MMP and/or TIMP.

What is arteriolosclerosis?

Hardening of small arteries and arterioles, and may cause downstream ischemic injury.

Describe the appearance of hyaline arteriolosclerosis.

Homogeneous, pink hyaline thickening with associated luminal narrowing.

What effect does hypertension have on the vasculature?

Hypertension accelerates atherogenesis and causes degenerative changes in the walls of large and medium arteries.

What is the most common condition associated with the development of aneurysms of the ascending aorta?

Hypertension.

Which condition is common to both anatomic variants of arteriolosclerosis?

Hypertension.

Why is it critically important to distinguish between infectious and immunological mechanisms of vasculitis?

Immunosuppressive therapy is appropriate for immune- mediated vasculitis but can worsen infectious vasculitis.

What is a true aneurysm?

Intact attenuated arterial wall or thinned ventricular wall of the heart bulges outwards.

List the factors that cause aneurysms due to loss of smooth muscle cells or inappropriate synthesis of non-collagenous or non-elastic extracellular matrix (1).

Ischemia.

What is a berry aneurysm?

It is a sac-like outpouching in a cerebral blood vessel, which can seem berry-shaped, hence the name. Once a berry aneurysm has formed it is likely to rupture, causing a stroke. Thus they are serious medical emergencies, and should be treated as soon as possible.