11. Blood vessels

Question 1

Name three forms of small vessel diseases that are hypertension-related.

(two are anatomic variants of arterioLOsclerosis)

Answer 1

Hyaline arteriolosclerosis: deposition of hyaline and matrix around vessels; age, HTN and diabetes. When in the kidneys it’s called nephrosclerosis - the arteriolar narrowing causes impairment of blood supply and glomerular scarring.

Hyperplastic arteriolosclerosis: laminated onion-skin fibrosis with luminal narrowing.

Pulmonary hypertension: caused by left heart failure, congenital heart disease, valve disorders, obstructive or interstitial lung disease, recurrent thromboemboli; arterioles show range of changes from intimal thickening to medial hyperplasia.

Robbins p. 492- 493

Question 2

List four causes of “secondary” hypertension.

Answer 2

Renal: acute glomerulonephritis, chronic renal disease, polycystic disease, renal artery stenosis, renal vasculitis, renin-producing tumors.

Endocrine: pheochromocytoma, hyperthyroidism, preeclampsia, adrenocortical dysfunction (Cushing etc), exogenous hormones.

Cardiovascular: coarctation of aorta, polyarteritis nodosa, increased volume or cardiac output, rigid aorta

Neurogenic: psychogenic, increased ICP, sleep apnea, acute stress (including surgery).

Table 11.2, p. 490.

Question 3

Name the four major patterns of arteriosclerosis.

Answer 3

1. Arteriolosclerosis (hyaline and hyperplastic, also pulmonary HTN)
2. Monckeberg medial sclerosis: medial calcification of muscular arteries; not clinically significant.
3. Fibromuscular intimal hyperplasia: the major rate-limiting factor in solid organ transplant. Occurs in muscular arteries larger than arterioles.
4. Atherosclerosis: intimal-based, chronic inflammatory and healing response of arterial wall to endothelial injury.
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Question 4

List non-modifiable and modifiable risk factors for atherosclerosis.

Answer 4

1. Non-modifiable: genetics, family history, age, male gender
2. Modifiable: hyperlipidemia, HTN, cigarette smoking, diabetes, inflammation.

Question 5

What are the three most important causes of endothelial dysfunction?

Answer 5

Hyperlipidemia

Hemodynamic disturbances (areas with nonlaminar flow, like branch points)

Inflammation

Robbins p. 498

Question 6

In order from most to least, which vessels are most extensively involved in atherosclerosis?

Answer 6

1. lower abdominal aorta and iliac arteries
2. coronary arteries
3. popliteal
4. internal carotid
5. circle of Willis

Robbins p. 501

Question 7

What are the 4 principal components of atherosclerotic plaques?

Answer 7

1. Cells: smooth muscle cells, macrophages, T-lymphocytes
2. Extracellular matrix (ECM): collagen, elastic fibers and proteoglycans;
3. Intracellular and extracellular LIPIDS
4. Calcifications (in later stage plaques)

(atherosclerosis is an intimal-based lesion composed of a fibrous cap and an atheromatous core; the constituents of the plaque include smooth muscle cells, extracellular matrix, lipids, inflammatory cells, and necrotic debris)

Question 8

List the 8 steps in the pathogenesis of atherosclerosis.

Answer 8

Endothelial injury and dysfunction

accumulation of lipoproteins

monocyte adhesion to the endothelium –> transformation into macrophages and foam cells

Platelet adhesion

Factor release

Smooth muscle cell proliferation, ECM production, and recruitment of T cells

Lipid accumulation

Calcification of ECM and necrotic debris (late)

Question 9

List 4 major conseqences of atherosclerosis.

Answer 9

Myocardial infarction

cerebral infarction

peripheral vascular disease

aortic aneurysms

also: mesenteric occlusion with bowel ischemia, sudden cardiac death, chronic ischemic heart disease,, ischemic encephalopathy, intermittent claudication are all consequences of flow-limiting stenosis that can be caused by atherosclerosis.

Question 10

List 3 changes that can occur in an atherosclerotic plaque

Answer 10

Rupture/fissuring: activates coagulation and induces thrombogenesis

Erosion/ulceration: exposes basement membrane (less frequently thrombogenic)

Hemorrhage: expands volume of plaque

Question 11

What is the gene and protein affected in Marfan syndrome?

Answer 11

Gene Fibrillin 1 (FBN1)–> Fibrillin protein

Defect results in inability to appropriately sequester TGF-B; loss of scaffolding.

Question 12

What are the two most important causes of aortic aneurysms?

Answer 12

Hypertension and Atherosclerosis

Question 13

Name 3 “subtypes” of abdominal aortic aneurysms.

Answer 13

Inflammatory: young patients, elevated ESR, lymphoplasmacytic inflammation with giant cells with periaortic scarring into anterior retroperitoneum; presumed localized immune response to aortic wall.

IgG-4 related: storiform fibrosis, IgG4 plasma cells; affects many organs, including the aorta. Response to steroids.

Mycotic AAA: can result from septic embolus (usually from infective endocarditis), extension of adjacent suppurative process, or circulating organisms directly infecting the aortic wall. Suppuration further destroys the media, leading to rapid dilation and rupture.

Question 14

List 3 conditions associated with aortic dissection

Answer 14

Marfan

Hypertension (major risk factor)

Pregnancy (rare)

*** aneurysm and dissection result from structural weakness of the vessel caused by aberrant TGF-B signalling, loss of smooth muscle cells, or changes in the extra-cellular matrix, which can result from ischemia, genetic defects, or defective matrix remodeling.

Question 15

What are the 3 anatomic classifications of aortic aneurysms?

Answer 15

DeBakey 1 : entire length of aorta

DeBakey 2: Ascending aorta only (1 & 2 are also called type A, and both involve the ascending aorta, either diffusely or in isolation)

DeBakey 3: Descending aorta only. (type B: after takeoff of great vessels from aorta)

Question 16

What are the two pathogenic mechanisms of vasculitis?

Answer 16

1. Immune-mediated inflammation

2. Direct invasion of vascular walls by infectious pathogens.

Question 17

What are the 4 main immunologic mechanisms underlying non-infectious vasculitis?

Answer 17

Immune complex deposition
Anti-neutrophil cytoplasmic antibodies (ANCAs)
Anti-EC antibodies (endothelial cell)
Autoreactive T-cells

Question 18

Name two types of vasculitis associated with immune complex deposition.

Answer 18

Drug hypersensitivity reactions : most commonly skin lesions.

Vasculitis secondary to infections : eg. polyarteritis nodosa = immune complexes composed of hepatitis B surface antigens (HBsAg) and anti-HBsAg antibody.

Question 19

List the antibodies associated with:

1. granulomatosis with polyangiitis
2. Churg-Strauss (allergic granulomatosis and angiitis)

Answer 19

1. GPA/Wegener: c-ANCA –> new name is anti-proteinase 3 (PR3-ANCA)
2. Churg-Strauss: p-ANCA –> anti-myeloperoxidase / anti-MPO (new name) ; also seen in leukocytoclastic vasculitis.
3. NB: most cases of leukocytoclastic vasculitis are ANCA-associated vasculitis, most commonly MPO-ANCA.

Question 20

list vessels that can be involved in giant cell arteritis.

Answer 20

Temporal arteries (most common; NB: requires 1cm biopsy because often focal)

Vertebral
Ophthalmic
Aorta (NB: patients under 50 - call it Takayasu, over 50 call it giant cell)

Robbins p. 511 - 512)

Question 21

What are the classic histologic findings of giant cell arteritis.

Answer 21

Intimal thickening

Granulomatous inflammation of MEDIA

Infiltrate of T-cells (CD4 >CD8)

Elastic lamina fragmentation

Question 22

List three clinical/pathological features that characterize Granulomatosis with polyangiitis (formerly Wegener’s).

Answer 22

1. Acute necrotizing GRANULOMAS of the upper respiratory tract (ear, nose, sinuses, throat) or the lower respiratory tract (lung) or both;
2. Necrotizing granulomatous VASCULITIS affecting small-medium sized vessels (capillaries, venules, arterioles, arteries), mostly in lung and upper airways;
3. Focal necrotizing, often crescentic, GLOMERULONEPHRITIS.

Question 23

List 3 organs that can be involved in GPA / Wegeners.

Answer 23

Lungs: bilateral pneumonitis with nodules and cavitary lesions; necrotizing granulomas that cavitate;

Kidneys: focal and segmental necrotizing glomerulonephritis, or crescentic glomerulonephritis

Nasopharynx: sinusitis and mucosal ulcerations

Question 24

List 4 organs that are commonly involved in Churg-Strauss.

Answer 24

1. Skin: palpable purpura
2. GI tract: bleeding
3. Kidneys: focal & segmental glomerulosclerosis
4. Heart: cardiotoxicity due to infiltrates of eosinophils often leads to cardiomyopathy.

NB: this disease shows striking eosinophilic infiltration of vessels and tissues; the above 4 are the most common and relevant manifestations.

Question 25

what is the major risk factor for Buerger’s disease?

Answer 25

SMOKING

Thromboangiitis obliterans (Buerger’s) is characterized by segmental, thrombosing, acute and chronic inflammation of medium/small arteries, especially TIBIAL and RADIAL… occurs almost exclusively in heavy smokers <35.

Question 26

What are characteristic histologic findings of Buerger/thromboangiitis obliterans?

Answer 26

Small and medium arteries, especially radial and tibial, with acute and chronic inflammation

luminal thrombosis

thrombosis may contain neutrophilic microabscesses

***UNIQUE FEATURE: unlike other vasculitides, the inflammatory process extends into contiguous veins and nerves; with time all three structures can be encased in fibrous tissue.

Question 27

List the 4 types of Kaposi Sarcoma.

Answer 27

1. Classic: mediterranean men, lower extremity skin nodules.
2. Endemic (African): HIV-NEGATIVE, young patients; involves lymph nodes and viscera. Poor prognosis.
3. Transplant-associated: immunosuppressed patients; lymph nodes, mucosa, viscera.
4. AIDS-associated (epidermic): AIDS-defining illness. Lymph nodes, dissemination to viscera.

Virtually all KS are infected by HHV-8.