CPR 9.13 Vascular Pathology

Question 1

Describe the common causes and histologic findings of hyaline arteriosclerosis

Answer 1

1. Def: hardening of small arteries and arterioles.
2. Clinical Presentation: Chronic HTN, diabetic microangiopathy.
3. Histology: homogenous, pink hyaline thickening of vessel wall due to plasma protein leakage across endothelial cells. Results in luminal narrowing.
   page 9

Question 2

Describe the common causes and histologic findings of hyper plastic arteriosclerosis.

Answer 2

1. Def: hardening of small arteries and arterioles.
2. Clinical Presentation: malignant HTN.
3. Histology: “onion skinning” due to concentric laminated thickening of vssel walls with lminal narrowing. Fibrinoid deposits and vessel wall necrosis.
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Question 3

Describe the 5 step progression of atherosclerosis.

Answer 3

1. Chronic endothelial injury
2. Endohelial dysfunction. Monocyte adhesion and emigration
3. Smooth muscle emigration from media to intima, macrophage activation.
4. Macrophages and smooth muscle cells engulf lipid
5. Smooth muscle proliferation, collegen and ECM deposition, EC lipid.

Question 4

Describe the early gross and micro pathology of atherosclerosis.

Answer 4

Page 19-20

1. Gross: Fatty streaks which are lipid-laden macrophages and SMC’s. Complicated plaques (calcified, fissured, ulcerated)
2. Micro: Fibrous cap of leukocytes, SMC’s, Dense CT over necrotic core.

Question 5

Describe the late gross and micro pathology of atherosclerosis.

Answer 5

D. Late Morphology p. 22→

1. Gross: Advanced atheromatous plaques.
2. Micro: internal and external elastic membranes are destroyed and media of the artery is thinned. (Vulerable cap: fibrous cap is thin, large lipd core with greater inflammation).

Question 6

Describe the 3 types of Aneurysms

Answer 6

A. True aneurysm (saccular type): the wall focally bulges outward but it otherwise intact.
B. True Aneurysm (fusiform type): circumferential dilation of the vessel without rupture.
C. False Aneurysm: the wall is reuptured, collection of blood (hematoma) bounded externally by adherent extravascular connective tissue.

Question 7

Atherosclerosis and HTN are associated with aneurysms in what locations respectively?

Answer 7

1. Atherosclerosis: strong factor in abdominal aortic aneurysms. (most commonly between renal arteries and iliac bifurcation.
2. HTN: strong factor in aneurysms of ascending aorta.

Question 8

Define an aortic dissection, the common etiologies in chronic and acute cases, and the associated pathology.

Answer 8

B. Etiologies: Seen in HTN’ve men 40-60 yoa. Younger populations with CT disorders like Marfan’s or Ehler’s). Trauma, infection, or diagnostic complication. C. Pathology: Cystic medial degneratioin. P. 41

Question 9

Describe the stanford classification system and clinical presentation of aortic dissection.

Answer 9

D. Stanford Classification:
1. Type A: ascending aorta (more common)
2. Type B: Distal to subclavian
E. Clinical Presentation: sudden, excruciating pain of anterior chest radiating betwee scapulae.

Question 10

Wegener Granulomatosis, Microscopic Polyangiitis, and Churg-Struass syndrome are all examples of what type of Vasculitic disease?

Answer 10

Small Vessel Pauci immune vasculitis

Question 11

Giant cell arteritis and Takayasu arteritis are examples of what type of Vasculitic disease?

Answer 11

Large Vessel vasculitis

Question 12

Polyarteritis nodosa, Kawasaki disease, and Buerger disease are examples of what type of Vasculitic disease?

Answer 12

Medium Vessel vasculitis

Question 13

Describe the etiology, clinical presentation, unique lab tests, histologic findings, and course of disease for Wegener Granulomatosis (GPA)

Answer 13

1. Etiology: unknown, may be inhaled environemntal agents.
2. Clinical Presentation: Male caucasion with Sinusitis, pulmonary infiltrate, and glomerulonephritis.
3. Lab Tests: T-cell mediated hypersensitivity reaction. 90-95% have PR3-ANCA autoantibodies. Leukocytosis, thrombocytosis, anti-GBMnegative. Can have hematurie, proteinuria, red cell casts, elevated BUN and creatinine with kidney involvement.
4. Histologic Findings: Necrotizing vasculitiis, geographic necrosis, granulomas. P. 51
5. Course of disease: 80% die within 1 year without treatment. 90% response to immunosuppression.

Question 14

Describe the etiology, clinical presentation, unique lab tests, histologic findings, and course of disease for Microscopic polyangiitis

Answer 14

1. Etiology: Offending agent such as Drug, microorganism, or heterologous protein.
2. Clinical Presentation: can be confined to skin or involve lung, heart, kidney, brain.
3. Lab Tests: Strongly associated with MPO-ANCA. Proteinuria and hematuria. Nodules, infiltrates, or alveolar hemorrhage on CXR.
4. Histologic Findings: Necrotizing vasculitis of small vesssels, usually capillaries. All lesions of same age. P. 54
5. Course of disease: Resolves with removal of offending agent.

Question 15

Describe the clinical presentation, unique lab tests, histologic findings, for Churg-Strauss syndrome

Answer 15

2. Clinical Presentation: asthma, allergic rhinitis, lung infiltrates, peripheral eosinophila, extravascular necrotizing granulomas. Multisystemic.
3. Lab Tests: Mild association with MPO-ANCA.
4. Histologic Findings: necrotizing vasculitis with granulomas and eosinophils. P. 56

Question 16

Describe the etiology, clinical presentation, unique lab tests, histologic findings, for Giant cell arteritis

Answer 16

1. Etiology: unknown. Affects large and medium size arteries espeically temporal, vertebral, and opthlamic.
2. Clinical Presentation: 2:1 Female to male. Headache and facial pain, visual prolems even blindness. Polymylagia rheumtica.
3. Lab Tests: ESR increased. Normocytic normochoromic anemia, ↑ alkaline phosphatase.
4. Histologic Findings: focal and segmental granulomatous inflammation in active disease. Scarring and intimal thickening in healed disease. P. 59->

Question 17

Describe the etiology, clinical presentation, unique lab tests, histologic findings, for Takayasu arteritis

Answer 17

1. Etiology: Unknown. Invlves medium to large arteries. Especially aortic arch and major branches.
2. Clinical Presentation: young females. Fever, malaise, night sweats, weight loss, occular issues, weak upper extremity pulses.
3. Lab Tests: ESR increased.
4. Histologic Findings: nonspecific. P. 64

Question 18

Describe the etiology, clinical presentation, histologic findings for Polyarteritis nodosa

Answer 18

1. Etiology: Males 2:1. May be associated with HBV infection, Type III hypersensitivity.
2. Clinical Presentation: Related to tissue involved. Often fever, malaise, and weight loss.
3. Lab Tests
4. Histologic Findings: Lesions seen in various stages of development. Found in any organ EXCEPT lung. Commonly renal and visceral vessels. . 69
   (a) Acute: fibrinoid necrosis of arterial wall
   (b) Chronic: granulation tissue and thrombosis.

Question 19

Describe the etiology, clinical presentation, unique lab tests, histologic findings, and course of disease for Kawasaki disease

Answer 19

1. Etiology: Unknown. Patients have numerous imunoregulatory problems suc as T cell activation, autoantibodies to endothelial cells, and circulating immune complexes. Affects medium sized arteries.
2. Clinical Presentation: Usually less than 4 yoa. Fever, desquamating skin rash, lymphadenopathy, oral erythema (Strawberry tongue), conjunctival erythem. .
3. Lab Tests: anti-endothelial cell antibodies.
4. Histologic Findings: Necrotizing vasculitis with fibrinoid necrosis. Lesions seen in various stages of development.
5. Course of disease: Acute, self limiting illness.

Question 20

Describe the etiology, clinical presentation, unique lab tests, histologic findings, and suggested treatment for Beurger disease (thromboangiitis obliterans)

Answer 20

1. Etiology: seen in heavy smokers often before age 35. Cause unknown.
2. Clinical Presentation: Nodular phlebitis, then Raynaud-like cold sensitivity and leg claudication. Pain and ganrene of extremities.
3. Lab Tests
4. Histologic Findings: segmental thrombosis with acute and chronic vasculitis of medium and small artereis and veins in extremities. P. 75
5. Course of disease: STOP SMOKING

Question 21

Describe the pathophysilogy of ANCA.

Answer 21

A. ANCA Definition: Many patients with vasculitis have circulating antibodies that react with neutrophil cytoplasmic antigens, so-called antineutrophil cytoplasmic antibodies (ANCAs) . ANCAs are a heterogeneous group of autoantibodies directed against constituents (mainly enzymes) of neutrophil primary granules, monocyte lysosomes, and endothelial cells. ANCAs are very useful diagnostic markers; their titers generally mirror clinical severity, and a rise in titers after periods of quiescence is predictive of disease recurrence.

Question 22

Discuss the pathophys of PR3-ANCA, an example, and how to test for it.

Answer 22

B. PR3-ANCA’s (cANCA): antibodies directed against enzymes with primary (azurophilic) granules in neutrophils, lysozymes of monocytes, and endothelial cells, expressing PR3.

1. Example: Polyangiitis (Wegener’s)    2. Test: ELISA for PR-3 AB’s.

Question 23

Discuss the pathophys of MPO-ANCA, examples, and how to test for it.

Answer 23

C. MPO-ANCA’s (pANCA): antibodies against myeloperoxide granules in lysosomes of neutrophils.

1. Example: Microscopic polyangitis and Churg-Strauss syndrome.
2. Test: ELISA for MPO aAB’s.