Pathology: Vascular Diseases

Front 1

Discuss Arteriovenous Fistulas:
congenital--
acquired--

Back 1

*Congenital – especially important in the brain!
-Symptoms will be due to pressure or rupture.

*Acquired:
-Trauma.
-Breakdown of walls:
1) Tumors
2) Infection (abscess).

-Iatrogenic:
1) Intentional as in dialysis patients.
2) Unintentional as a postoperative or post catheterization complication.

Front 2

List the types of Vasculitides: 10

Back 2

*Giant cell (temporal) arteritis
*Takayasu arteritis
*Polyarteritis nodosa
*Kawasaki disease
*Microscopic polyangiitis/polyarteritis
*Churg-Strauss syndrome
*Wegener granulomatosis
*Thomboangiitis obliterans
*In collagen vascular diseases
*Infectious

Front 3

Discuss Vasculitis in general:
etiology--
noninfectious vasculitis--

Back 3

*Etiology:
1) Infectious, noninfectious, or unknown.

2) Noninfectious vasculitides:
-Referred to as systemic necrotizing vasculitides.
-Most are due to immunological mechanisms.
-Classified by the size of involved vessels.

*Mostly we are talking about arteritis but veins can also be involved.

Front 4

Vasculitis: what's the evidence for an immunological role?

Back 4

*Similar lesions seen in experiments involving immune-complex mediation.

*Immune reactants, complement found in serum of symptomatic patients:
-DNA-anti-DNA immune complexes in SLE.
-IgG, IgM, and complement are elevated in cryoglobulinemic vasculitis.

*Hypersensitivity to drugs is implicated in 10% of vasculitic skin lesions: biopsies demonstrate complexes deposited in vessel walls.

*Viral infection-associated vasculitis:
-HepB surface antigen (HBSAg) and HBsAg-anti-HBsAg immune complexes, with complement, in serum and in vascular lesions of those patients.
-Vasculitis will REMIT with immunosuppression, even if the infection persists.

*Glomerulonephritis (a vasculitis!) in chronic HCV infection:
-HCV/RNA and cryoprecipitates with anti-HCV antibodies in glomeruli.

Front 5

Discuss Antineutrophil Cytoplasmic Antibodies (ANCA):
why are they useful?

Back 5

*A heterogeneous group of autoantibodies.

*React to enzymes in azurophilic granules in neutrophils (and related enzymes in other cells).

*They are useful diagnostic markers in small vessel vasculitides, via indirect immunofluorescence.

Front 6

What are the categories of IF staining with ANCA? What is each one useful for?

Back 6

*c-ANCA – cytoplasmic staining:
1) Wegener granulomatosis.

*p-ANCA – perinuclear staining:
1) microscopic polyangiitis.
2) Churg-Strauss syndrome.

Front 7

Describe the process of using ANCA to detect antibodies:

Back 7

*Patient’s serum --> incubated with normal neutrophils --> Slides stained using fluorescent-labeled anti-human Ig.

Front 8

How are Vasculitides diagnosed?
3 things to consider.

Back 8

*Size of vessels involved.
*Histologic findings.
*Clinical presentation.

Front 9

List the Classic Vasculitides:

Back 9

*LARGE:
-Giant cell (temporal) arteritis.
-Takayasu arteritis.

*Medium:
-Polyarteritis nodosa.
-Kawasaki disease.

*small:
-Microscopic polyangiitis/polyarteritis.
-Churg-Strauss syndrome.
-Wegener granulomatosis.

Front 10

Discuss Giant Cell (Temporal) Arteritis in general:

Back 10

*Most common vasculitis.

*Classified as a large vessel vasculitis:
-Can affect aorta.
-Predominantly affects medium-sized and small arteries, especially the cranial arteries.

*Disease of older people (>50).

*Temporal, opthalmic, facial arteries most commonly affected.

Front 11

Gross and Histologic traits of Giant Cell (Temporal) Arteritis:

Back 11

*Gross – nodular swellings (beading), marked narrowing of lumen, thrombi can develop.

*Histology - 2 patterns:
1) granulomatous inflammation in media near internal elastic membrane (IEM), with giant cells and lymphocytes.
2) nonspecific arteritis with no giant cells.

Front 12

Back 12

L: Temporal artery. Giant cell pointed to by arrow.
Middle: Elastic stain. IEM is damaged.

*Giant Cell (Temporal) Arteritis.

Front 13

Back 13

*Lumen of artery at left. Arrow points to giant cell.
*Note granuloma and inflammatory cells.
*Giant Cell (Temporal) Arteritis.

Front 14

Discuss Takayasu Arteritis in general:
who does it affect?

Back 14

*Classified as a large vessel vasculitis:
-Affects the aorta.
-Also affects the medium-sized branches of the aortic arch.
-Occasionally, the pulmonary artery involved.

*“Pulseless disease” – Affects the upper extremities!

*Mostly affects young women (<40).

*In some cases, may result in aneurysmal dilation of ascending aorta, aortic valve regurgitation, dissection.

Front 15

Back 15

*Takayasu Arteritis
*Arrows point to constrictions.
*Usually multiple constrictions.

Front 16

Gross and Histologic traits of Takayasu Arteritis:

Back 16

*Adventitial and medial mononuclear infiltrate.
*Perivascular cuffing of vasa vasorum.
*Giant cells and foci of medial necrosis.

*Histologically, hard to distinguish from temporal (giant cell) arteritis and lues (syphilitic lesions).

Front 17

Back 17

*Takayasu Arteritis.
*Note swollen appearance of vessel on right.
*Histology is vague; can't distinguish from Giant Cell Arteritis.

Front 18

Back 18

*Takayasu Arteritis.
*Note adventitial inflammation. Intima and media can get kind of wrinkly and funny, but are not as affected as the adventitia.

Front 19

Back 19

*Takayasu Arteritis.
*Note giant cell.

Front 20

Back 20

*Takayasu Arteritis.

Front 21

Discuss Polyarteritis Nodosa (PAN) in general:

Back 21

*Medium vessel vasculitis (medium to small arteries).
*Segmental, not circumferential involvement of arteries.
*“Nodules” develop (aneurysmal dilatations).
*NO involvement of arterioles (NO glomerulonephritis).

*Not usually ANCA positive.
*ABSENT or MINIMAL immune complex deposition.

*Multiorgan involvement:
-KIDNEYS in 85%, HEART in 75% (plus liver in 60%, GI tract in 50%, muscle in 40%, pancreas in 35%, also testes, peripheral nerves , CNS, and skin).

*Lungs NOT involved.

Front 22

Back 22

*Skin involvement and wrist drop due to nerve involvement in Polyarteritis Nodosa.

Front 23

Back 23

*Polyarteritis Nodosa: Acute Phase:
-Transmural infiltration by polys, eosinophils, and lymphocytes.
-Fibrinoid necrosis of vessel wall.
-Note sparing of portion of circumference.

Front 24

Back 24

*Polyarteritis nodosa: segmental involvement with portion of vessel wall preserved.

Front 25

Back 25

*Polyarteritis nodosa – kidney (not a glomerulonephritis).
*Arrow denotes artery with huge amount of inflammation around it. Glomeruli are visible and are NOT affected.

Front 26

Back 26

*Polyarteritis Nodosa; Healed Lesion:
-Wall has been replaced by cellular connective tissue.
-Lumen is small and eccentric.

Front 27

Discuss Kawasaki Disease in general:
AKA?
Who does it affect??
What is it associated with?

Back 27

*Medium vessel vasculitis.
*A.K.A. mucocutaneous lymph node syndrome.

*Affects children.
*Appears in clusters, may be autoimmune.

*Usually associated with fever, oral and conjunctival erythema/erosion, erythema of palms and soles, rash, enlarged cervical lymph nodes.

Front 28

Kawasaki Disease:
Discuss pathological changes--

Back 28

*An acute necrotizing vasculitis of entire wall.

*May involve coronaries, with later development of aneurysms!

*Tendency to form occlusive thrombi.
*Can result in MI or sudden death.

*Due to anti-endothelial cell antibodies!

Front 29

Back 29

*Kawasaki Disease: Cross-section of an aneurysmal coronary artery with occlusive thrombus. 6 month old child with acute, massive MI.

Front 30

Discuss Microscopic Polyangiitis in general:

Back 30

*Small vessel vasculitis.
*Restricted to arterioles, capillaries, and venules.

*Lung involved.

*Kidney involved; necrotizing glomerulonephritis.

Front 31

Histology and ANCA association of Microscopic Polyangiitis:

Back 31

*Histology:
-Wall infiltrated with neutrophils.
-Fibrinoid necrosis.
-No granulomas.

*Strong association with p-ANCA.

Front 32

Back 32

*Cutaneous leukocytoclastic vasculitis: clinically shows as purpura. Polys infiltrate vascular wall and surrounding tissue, with fragmentation of nuclei--> “nuclear dust.”

*Fibrin and immunoglobulin deposition imparts a smudgy appearance.

*Small, round, purple dots are fragments of polys.

Front 33

Discuss Churg-Strauss Syndrome in general:

Back 33

*Small vessel vasculitis.

*Patients have peripheral blood eosinophilia.
*Likely to involve respiratory system (asthma).

*Strong association with p-ANCA.

Front 34

Histology in Churg-Strauss Syndrome:

What distinguishes it from polyarteritis nodosa and microscopic polyangiitis?

Back 34

*In some ways is similar to polyarteritis nodosa and microscopic polyangiitis:
-Wall infiltration by neutrophils.
-Fibrinoid necrosis in vessel wall.

*But also has:
-Granulomas.
-Eosinophils in walls and surrounding tissue.

Front 35

Back 35

*Churg-Strauss syndrome.
*Lung tissue. Some alveoli (arrow) have dense accumulations of inflammatory cells. Eosinophils and neutrophils.

Front 36

Back 36

*Churg-Strauss Syndrome.
*Fibrinoid necrosis of artery.
*Bordered by granulomatous inflammation.
*Surrounded by eosinophils.

Front 37

Back 37

*Churg-Strauss Syndrome.
*Bordered by granulomatous inflammation.

Front 38

Discuss Wegener Granulomatosis in general:

Back 38

*Small vessel vasculitis.
*Small to medium-sized arteries and veins.
*Respiratory and renal involvement.

*Strong association with c-ANCA.

Front 39

What distinguishes Wegener Granulomatosis?

Back 39

*Necrotizing vasculitis.

*Characterized by a triad:
-Acute necrotizing granulomas (respiratory tract – upper, lower, or both).
-Focal necrotizing, granulomatous vasculitis (most prominent in respiratory tract).
-Focal or crescentic glomerulonephritis.

*Granulomas are vascular and extravascular.

*Must rule out TB and fungal infection.

Front 40

Back 40

*Wegener Granulomatosis.
*Large, nodular, caseous lesions in the lung. Look an awful lot like TB.
*Similar lesions develop in the upper respiratory tract.

Front 41

Back 41

*Left: Granulomatous inflammation surrounding a blood vessel and a bronchus.
*Mid: Perivascular granuloma (top left) with central necrosis.
*Right: A granuloma with central necrosis and giant cell (arrow).

Front 42

Back 42

*Wegener Granulomatosis.
*Granulomatous inflammation adjacent to small artery vasculitis.
*Giant cells at arrows.

Front 43

Discuss Thromboangiitis Obliterans:

Back 43

*A.K.A. Buerger disease; a disease of young smokers.

*Segmental acute/chronic inflammation, occasionally with giant cells.

*Thromboses in medium and small arteries, especially the radial and tibial arteries.

*Inflammation may extend to veins and nerves.

Front 44

Back 44

*Thromboangiitis Obliterans.
*A.K.A. Buerger disease; a disease of young smokers.

Front 45

Back 45

*Thromboangiitis obliterans with microabscess in vessel wall.
*Note elastic lamina.

Front 46

Back 46

*Top: Acute lesion of Buerger’s disease in a vein with intense thromboangiitis, showing a microabscess in the thrombus with two multi-nucleated giant cells (arrows).

*Bottom: Vessel thromboses, neutrophils in wall of artery and adjacent veins. With time, there will be recanalization.

Front 47

Describe Vasculitis in other diseases:
arthritis--
SLE--
others--

Back 47

*Rheumatoid arthritis: small and medium arteries; occasionally aorta.

*Lupus erythematosis or related lupus anticoagulant with antiphospholipid antibody.

*Malignancy.

*Mixed cryoglobulinemia.

*Henoch-Schönlein purpura.

Front 48

Back 48

*Epicardial coronary artery with organized thrombus following vasculitis.
*Young woman with anti-phospholipid antibody (SLE).

Front 49

Discuss Infectious Arteritis:

Back 49

*Vessel walls can be involved in bacterial pneumonia, tuberculous lesions, abscesses, meningitis.
*Focal infectious arteritis with septic emboli or septicemia.
*If the wall expands – mycotic aneurysm.

*Fungi may also cause infectious arteritis, especially Aspergillus and the organisms of mucormycosis.

Front 50

What's the ∆ b/t true and false aneurysms?

Back 50

*True aneurysm: Localized dilation in which all 3 layers of vessel wall or heart are involved.

*False aneurysm: Extravascular hematoma ommunicating with lumen or chamber, due to rupture of wall of vessel or heart chamber.

Front 51

Discuss True aneurysms:

Back 51

*Weakened vessel wall is due to genetic or acquired disease.

*Most common cause = atherosclerosis.
-Atherosclerosis thins the media.

*In aorta, the abdominal portion is most affected:
-Is most severely involved by atherosclerosis.
-Is the most common site of aneurysm formation.
-Abdominal aortic aneurysm - AAA.

*Fortunately usually infrarenal. Kidneys get enough blood flow.

Front 52

Shapes of true aneurysms?

Back 52

*Saccular –
involve a portion of circumference and are spherical; often filled with thrombus.

*Fusiform –
shaped like a spindle, tapered at both ends - involve entire circumference.

Front 53

Back 53

AAA.

Front 54

How do you fix an AAA?

Back 54

*OR you can graft a repair.

Front 55

Back 55

L: Aneurysm of the brachial artery.
Mid: Multiple thrombi in the lumen.
R: Saphenous vein graft replaces the brachial aneurysm.

Front 56

What are Berry Aneurysms?

Back 56

*A special group of saccular aneurysms.
*Thin-walled outpouchings at branch points in Circle of Willis; 1-3 mm.
*Wide or narrow neck.
*Rupture occurs at apex of sac--> can lead to SAH.

Front 57

Discuss Berry Aneurysms:
causes?
pathologic changes?

Back 57

*Frequent cause of subarachnoid hemorrhage; may involve brain tissue.

*Most cases sporadic.

*However, can be associated with:
1) Autosomal dominant polycystic disease (ADPKD).
2) Neuro-fibromatosis (NF) type 2.
3) Ehlers-Danlos syndrome.
4) Marfan syndrome.

*Wall of sac shows thick intima with absent or thin fragmented media.

Front 58

Discuss Syphilitic Aortitis:

Back 58

*Now rare, it is a prominent feature of tertiary syphilis (lues).

*Begins in adventitia:
-obliterative endarteritis of vasa vasorum.
-perivascular cuffing - lymphocytes, plasmas.

*Medial necrosis with loss of elastic fibers and smooth muscle.
*Dissection unlikely; medial fibrosis develops.

Front 59

Back 59

*Syphilitic aortitis - Perivascular Cuffing.

Front 60

Back 60

*Tree Barking in 3˚ syphilis.
*Not diagnostic of lues; can be seen in other vasculitides.
*Lighter part at top is the "tree bark."

Front 61

Discuss Aortic Dissection:

Back 61

*Blood enters a defective media through a tear in the intima.

*The media splits into inner and outer layers, for variable distances.

*Dissection can continue into the media of branching vessels (i.e. renal arteries from Abd Aorta).

*Dissecting blood can re-enter lumen or rupture into surrounding tissue or body cavity; e.g. pleural or pericardial.

Front 62

Back 62

*Aortic dissection - Intimal tear.
*Aortic valve is visible.

Front 63

Back 63

Front 64

Back 64

Dissection of Aorta to iliac artery.

Front 65

What causes aortic dissection?
How can we catch and prevent it?

Back 65

*Hypertension is the leading cause.

*In younger patients, due to rare diseases:
-genetically determined defects of collagen, fibrillin or elastin as in Marfan, Turner, or Ehlers-Danlos syndromes.

*“Cystic medial degeneration” may be preexisting lesion seen on histology:
-Misnomer: elastic tissue fragmentation with replacement by extracellular matrix material. Not truly cystic.

Front 66

Back 66

Medial degeneration; precursor of an aortic dissection.

Front 67

Back 67

*Aortic Dissection: Cystic medial degeneration (elastic-trichrome stain).
*Elastic tissue is not orderly.

Front 68

What's the DeBakey classification of aortic dissections?

Back 68

*Deals with which part of aorta is involved (ascending, descending, or both).

Front 69

Discuss complications of Aortic Dissection:

Back 69

*Dissection to aortic root distorts aortic valve and causes AV regurgitation.

*Dissection to aortic root with rupture into pericardial sac causes cardiac tamponade.

*Dissections can occur de novo in other arteries such as coronary, hepatic, splenic, renal, etc.

Front 70

One more time: 3 key things to bear in mind when diagnosing the Vasculitides:

Back 70

-Size of vessels involved.
-Histologic findings.
-Clinical presentation.