Vascular Pathology

Question 1

Vasculitis - basics

Answer 1

A. Inflammation of the blood vessel wall
1. Arterial wall is comprised of three layers: endothelial intima, smooth muscle media, and connective tissue adventitia (Fig. 7.1).

B. Etiology is usually unknown; most cases are not infectious.

C. Clinical features include
1. Nonspecific symptoms of inflammation (e.g., fever, fatigue, weight loss, and myalgias)
2. Symptoms of organ ischemia - due to luminal narrowing or thrombosis of the inflamed vessels

D. Divided into large-, medium-, and small-vessel vasculitides
1. Large-vessel vasculitis involves the aorta and its major branches.
2. Medium-vessel vasculitis involves muscular arteries that supply organs.
3. Small-vessel vasculitis involves arterioles, capillaries, and venules.

Question 2

LARGE-VESSEL VASCULITIS

Answer 2

A. Temporal (Giant Cell) Arteritis
1. Granulomatous vasculitis that classically involves branches of the carotid artery 2. Most common form of vasculitis in older adults (> 50 years); usually affects
females
3. Presents as headache (temporal artery involvement), visual disturbances (ophthalmic artery involvement), and jaw claudication. Flu-like symptoms with joint and muscle pain (polymyalgia rheumatica) are often present. ESR is elevated.
4. Biopsy reveals inflamed vessel wall with giant cells and intimal fibrosis (Fig. 7.2).
i. Lesions are segmental; diagnosis requires biopsy of a long segment of vessel, and a negative biopsy does not exclude disease.
5. Treatment is corticosteroids; high risk of blindness without treatment

B. Takayasu Arteritis
1. Granulomatous vasculitis that classically involves the aortic arch at branch points
2. Presents in adults < 50 years old (classically, young Asian females) as visual and neurologic symptoms with a weak or absent pulse in the upper extremity (‘pulseless disease’). ESR is elevated. 3. Treatment is corticosteroids.

Question 3

Temporal (Giant Cell) Arteritis

Answer 3

A. Temporal (Giant Cell) Arteritis
1. Granulomatous vasculitis that classically involves branches of the carotid artery 2. Most common form of vasculitis in older adults (> 50 years); usually affects
females
3. Presents as headache (temporal artery involvement), visual disturbances
(ophthalmic artery involvement), and jaw claudication. Flu-like symptoms with
joint and muscle pain (polymyalgia rheumatica) are often present. ESR is
elevated.
4. Biopsy reveals inflamed vessel wall with giant cells and intimal fibrosis (Fig. 7.2).
i. Lesions are segmental; diagnosis requires biopsy of a long segment of vessel,
and a negative biopsy does not exclude disease. 5. Treatment is corticosteroids; high risk of blindness without treatment

Question 4

Takayasu Arteritis

Answer 4

1. Granulomatous vasculitis that classically involves the aortic arch at branch
   points 2. Presents in adults < 50 years old (classically, young Asian females) as visual and
   neurologic symptoms with a weak or absent pulse in the upper extremity
   (‘pulseless disease’). ESR is elevated. 3. Treatment is corticosteroids.

Question 5

Medium vessel vasculitis

Answer 5

polyarteritis nodosa
Kawasaki disease
buerger disease

Question 6

Polyarteritis Nodosa

Answer 6

1. Necrotizing vasculitis involving multiple organs; lungs are spared.
2. Classically presents in young adults as hypertension (renal artery involvement),
   abdominal pain with melena (mesenteric artery involvement), neurologic disturbances, and skin lesions. Associated with serum HBsAg
3. Lesions of varying stages are present. Early lesion consists of transmural
   inflammation with fibrinoid necrosis (Fig. 7.3); eventually heals with fibrosis, producing a ‘string-of-pearls’ appearance on imaging
4. Treatment is corticosteroids and cyclophosphamide; fatal if not treated

Question 7

Kawasaki Disease

Answer 7

1. Classically affects Asian children < 4 years old
2. Presents with nonspecific signs including fever, conjunctivitis, erythematous
   rash of palms and soles, and enlarged cervical lymph nodes
3. Coronary artery involvement is common and leads to risk for (1) thrombosis
   with myocardial infarction and (2) aneurysm with rupture.
4. Treatment is aspirin and IVIG; disease is self-limited.

Question 8

Buerger Disease

Answer 8

1. Necrotizing vasculitis involving digits
2. Presents with ulceration, gangrene, and autoamputation of fingers and toes;
   Raynaud phenomenon is often present.
3. Highly associated with heavy smoking; treatment is smoking cessation.

Question 9

SMALL-VESSEL VASCULITIS

Answer 9

Wegener Granulomatosis
Microscopic Polyangitis
Churg-Strauss Syndrome
Henoch- Schonlein Purpura

Question 10

Wegener Granulomatosis

Answer 10

1. Necrotizing granulomatous vasculitis involving nasopharynx, lungs, and kidneys 2. Classic presentation is a middle-aged male with sinusitis or nasopharyngeal
   ulceration, hemoptysis with bilateral nodular lung infiltrates, and hematuria due
   to rapidly progressive glomerulonephritis.
2. Serum c-ANCA levels correlate with disease activity.
3. Biopsy reveals large necrotizing granulomas with adjacent necrotizing vasculitis
   (Fig. 7.4).
4. Treatment is cyclophosphamide and steroids; relapses are common.

Question 11

Microscopic Polyangiitis

Answer 11

1. Necrotizing vasculitis involving multiple organs, especially lung and kidney
2. Presentation is similar to Wegener granulomatosis, but nasopharyngeal
   involvement and granulomas are absent. 3. Serum p-ANCA levels correlate with disease activity. 4. Treatment is corticosteroids and cyclophosphamide; relapses are common.

Question 12

Churg-Strauss Syndrome

Answer 12

1. Necrotizing granulomatous inflammation with eosinophils involving multiple organs, especially lungs and heart
2. Asthma and peripheral eosinophilia are often present.
3. Serum p-ANCA levels correlate with disease activity .

Question 13

Henoch-Schönlein Purpura

Answer 13

1. Vasculitis due to IgA immune complex deposition; most common vasculitis in
   children 2. Presents with palpable purpura on buttocks and legs, GI pain and bleeding, and
   hematuria (IgA nephropathy); usually occurs following an upper respiratory
   tract infection 3. Disease is self-limited, but may recur; treated with steroids, if severe

Question 14

Hypertension -basics

Answer 14

A. Increased blood pressure; may involve pulmonary (see chapter 9) or systemic
circulation B. Systemic HTN is defined as pressure ≥ 140/90 mm Hg (normal ≤ 120/80 mm Hg);
divided into primary or secondary types based on etiology

Question 15

PRIMARY HTN

Answer 15

A. HTN of unknown etiology (95% of cases)
B. Risk factors include age, race (increased risk in African Americans, decreased risk in
Asians), obesity, stress, lack of physical activity, and high-salt diet.

Question 16

SECONDARY HTN

Answer 16

A. HTN due to an identifiable etiology (5% of cases)

B. Renal artery stenosis is a common cause (renovascular hypertension).
1. Stenosis decreases blood flow to glomerulus. 2. Juxtaglomerular apparatus (JGA) responds by secreting renin, which converts
angiotensinogen to angiotensin I.
3. Angiotensin I is converted to angiotensin II (ATII) by angiotensin converting enzyme (ACE).
4. ATII raises blood pressure by (1) contracting arteriolar smooth muscle,
increasing total peripheral resistance and (2) promoting adrenal release of
aldosterone, which increases resorption of sodium in the distal convoluted tubule
(expanding plasma volume).
5. Leads to HTN with increased plasma renin and unilateral atrophy (due to
low blood flow) of the affected kidney; neither feature is seen in primary
hypertension.

C. Important causes of stenosis include atherosclerosis (elderly males) and
fibromuscular dysplasia (young females).
1. Fibromuscular dysplasia is a developmental defect of the blood vessel wall,
resulting in irregular thickening of large- and medium-sized arteries,
especially the renal artery.

Question 17

BENIGN AND MALIGNANT HTN

Answer 17

A. HTN can also be classified as benign or malignant.

B. Benign HTN is a mild or moderate elevation in blood pressure; most cases of HTN
are benign. 1. Clinically silent; vessels and organs are damaged slowly over time.

C. Malignant HTN is severe elevation in blood pressure ( >180/120 mm Hg); comprises
< 5% of cases 1. May arise from preexisting benign HTN or de novo 2. Presents with acute end-organ damage (e.g., acute renal failure, headache, and
papilledema) and is a medical emergency

Question 18

Arteriosclerosis - basics

Answer 18

A. Literally, “hard arteries;” due to thickening of the blood vessel wall
B. Three pathologic patterns - atherosclerosis, arteriolosclerosis, and Mönckeberg
medial calcific sclerosis

Question 19

ATHEROSCLEROSIS

Answer 19

A. Intimal plaque that obstructs blood flow
1. Consists of a necrotic lipid core (mostly cholesterol) with a fibromuscular cap
(Fig. 7.5); often undergoes dystrophic calcification
B. Involves large- and medium-sized arteries; abdominal aorta, coronary artery,
popliteal artery, and internal carotid artery are commonly affected.

Question 20

Atherlosclerosis risk factors

Answer 20

Risk factors for atherosclerosis are divided into modifiable and nonmodifiable.
1. Modifiable risk factors include hypertension, hypercholesterolemia (LDL
increases risk; HDL decreases risk), smoking, and diabetes. 2. Nonmodifiable risk factors include age (number and severity of lesions increase
with age), gender (increased risk in males and postmenopausal females; estrogen
is protective), and genetics (multifactorial, but family history is highly predictive
of risk).

Question 21

Pathogenesis of atherosclerosis

Answer 21

. Damage to endothelium allows lipids to leak into the intima.
2. Lipids are oxidized and then consumed by macrophages via scavenger receptors,
resulting in foam cells.
3. Inflammation and healing leads to deposition of extracellular matrix and
proliferation of smooth muscle.

Question 22

morphologic stages of atherosclerosis

Answer 22

1. Begins as fatty streaks (flat yellow lesions of the intima consisting of lipid-laden
   macrophages); arise early in life (present in most teenagers)
2. Progresses to atherosclerotic plaque

Question 23

Complications of atherosclerosis

Answer 23

Complications of atherosclerosis account for> 50% of disease in Western countries.
1. Stenosis of medium-sized vessels results in impaired blood flow and ischemia
leading to i. Peripheral vascular disease (lower extremity arteries, e.g., popliteal)
ii. Angina (coronary arteries)
iii. Ischemic bowel disease (mesenteric arteries)
2. Plaque rupture with thrombosis results in myocardial infarction (coronary
arteries) and stroke (e.g., middle cerebral artery).
3. Plaque rupture with embolization results in atherosclerotic emboli, characterized
by cholesterol crystals within the embolus (Fig. 7.6).
4. Weakening of vessel wall results in aneurysm (e.g., abdominal aorta).

Question 24

Arteriolosclerosis

Answer 24

A. Narrowing of small arterioles; divided into hyaline and hyperplastic types

B. Hyaline arteriolosclerosis is caused by proteins leaking into the vessel wall,
producing vascular thickening; proteins are seen as pink hyaline on microscopy (Fig. 7.7).
1. Consequence of long-standing benign hypertension or diabetes
2. Results in reduced vessel caliber with end-organ ischemia; classically produces
glomerular scarring (arteriolonephrosclerosis, Fig. 7.8) that slowly progresses to chronic renal failure

C. Hyperplastic arteriolosclerosis involves thickening of vessel wall by hyperplasia of
smooth muscle (‘onion-skin’ appearance, Fig. 7.9).
1. Consequence of malignant hypertension 2. Results in reduced vessel caliber with end-organ ischemia 3. May lead to fibrinoid necrosis of the vessel wall with hemorrhage; classically
causes acute renal failure with a characteristic ‘flea-bitten’ appearance

Question 25

MÖNCKEBERG MEDIAL CALCIFIC SCLEROSIS

Answer 25

A. Calcification of the media of muscular (medium-sized) arteries; nonobstructive (Fig.
7.10A)

B. Not clinically significant; seen as an incidental finding on x-ray or mammography
(Fig. 7.10B)

Question 26

Aortic dissection

Answer 26

A. Intimal tear with dissection of blood through media of the aortic wall (Fig. 7.11)

B. Occurs in the proximal 10 cm of the aorta (high stress region) with preexisting
weakness of the media

C. Most common cause is hypertension (older adults); also associated with inherited
defects of connective tissue (younger individuals)
1. Hypertension results in hyaline arteriolosclerosis of the vasa vasorum; decreased
flow causes atrophy of the media. 2. Marfan syndrome and Ehlers-Danlos syndrome classically lead to weakness of
the connective tissue in the media (cystic medial necrosis).

D. Presents as sharp, tearing chest pain that radiates to the back E. Complications include pericardial tamponade (most common cause of death),
rupture with fatal hemorrhage, and obstruction of branching arteries (e.g., coronary
or renal) with resultant end-organ ischemia.

Question 27

THORACIC ANEURYSM

Answer 27

A. Balloon-like dilation of the thoracic aorta

B. Due to weakness in the aortic wall. Classically seen in tertiary syphilis; endarteritis
of the vasa vasorum results in luminal narrowing, decreased flow, and atrophy of the vessel wall. Results in a ‘tree-bark’ appearance of the aorta (Fig. 7.12)

C. Major complication is dilation of the aortic valve root, resulting in aortic valve
insufficiency. 1. Other complications include compression of mediastinal structures (e.g., airway
or esophagus) and thrombosis/embolism.

Question 28

ABDOMINAL AORTIC ANEURYSM

Answer 28

A. Balloon-like dilation of the abdominal aorta; usually arises below the renal arteries,
but above the aortic bifurcation (Fig. 7.13)

B. Primarily due to atherosclerosis; classically seen in male smokers > 60 years old with
hypertension
1. Atherosclerosis increases the diffusion barrier to the media, resulting in atrophy and weakness of the vessel wall.

C. Presents as a pulsatile abdominal mass that grows with time D. Major complication is rupture, especially when > 5 cm in diameter; presents with
triad of hypotension, pulsatile abdominal mass, and flank pain
1. Other complications include compression of local structures (e.g., ureter) and
thrombosis/embolism.

Question 29

HEMANGIOMA

Answer 29

A. Benign tumor comprised of blood vessels (Fig. 7.14)
B. Commonly present at birth; often regresses during childhood
C. Most often involves skin and liver

Question 30

ANGIOSARCOMA

Answer 30

A. Malignant proliferation of endothelial cells; highly aggressive

B. Common sites include skin, breast, and liver.
1. Liver angiosarcoma is associated with exposure to polyvinyl chloride, arsenic,
and Thorotrast.

Question 31

KAPOSI SARCOMA

Answer 31

A. Low-grade malignant proliferation of endothelial cells; associated with HHV-8

B. Presents as purple patches, plaques, and nodules on the skin (Fig. 7.15); may also
involve visceral organs

C. Classically seen in
1. Older Eastern European males - tumor remains localized to skin; treatment
involves surgical removal. 2. AIDS - tumor spreads early; treatment is antiretroviral agents (to boost immune
system). 3. Transplant recipients - tumor spreads early; treatment involves decreasing
immunosuppression.