Patho 3

Front 1

• Refers to inflammation and necrosis of blood vessels, including arteries, veins, and capillaries.
• Causes include infectious agents, mechanical trauma, radiation or toxins.
However, in many cases of vasculitis, no specific etiology is determined.

Back 1

vasculitis

Front 2

• Vasculitic syndromes are thought to involve immune mechanisms, including:
(1) the deposition of ____________,
(2) a direct attack on the vessels by circulating _________, and
(3) various forms of cell-mediated immunity.

Back 2

immune complexes

antibodies

Front 3

antigen w/corresponding antibody =

Back 3

immune complex

Front 4

may cause endothelial damage by activating neutrophils, and antibody titers correlate with disease activity.
•detected by indirect immunoflourescence assays using the patient's serum and ethanol-fixed neutrophils.

Back 4

ANCA

Front 5

• Small vessel vasculitides, like Wegener granulomatosis and Polyarteritis Nodosa, are associated with _____________ but the contribution of these autoantibodies to the vasculitis is not understood.
These may cause endothelial damage by activating neutrophils, and antibody titers correlate with disease activity.

Back 5

anti- neutrophil cytoplasmic antibodies (ANCA),

Front 6

• An acute, necrotizing vasculitis that affects medium and smaller-sized muscular arteries
• It occurs primarily in whites and is more common in men than in women.
• The overall incidence is not as common as compared to other vasculitides and affects many of the organs in the body.
• (if pt's don't get tx, they will die)

Back 6

Polyarteritis Nodosa (PAN)

Front 7

• The characteristic lesions within the muscular arteries are patchy in distribution, and may extend to renal, splenic or coronary arteries.
• The most prominent feature of the affected artery is an area of fibrinoid necrosis in which the medial muscle and adjacent tissue are fused into a eosinophilic mass of fibrin.
-A vigorous acute inflammatory response surrounds the area of necrosis and extends into all the other layers of the vessel.
• Neutrophils, plasma cells, and lymphocytes are present in varying proportions.

Back 7

Polyarteritis Nodosa (PAN)

Front 8

• Thrombosis of the smaller arteries is common and infarcts are usually found in the involved organs. Injury to larger arteries is associated with the formation of small aneurysms, particularly in the branches of the renal, coronary, and cerebral arteries.
• An aneurysm may rupture, and if located in a critical area, may cause a fatal hemorrhage.
• If the patient survives for several months, many of the vascular lesions will show evidence of healing with fibrosis of the media and gaps in the elastic laminae, especially if corticosteroids have been administered.

Back 8

Polyarteritis Nodosa (PAN)

Front 9

Polyarteritis Nodosa (PAN)
is associated with which ANCA

Back 9

P-ANCA

Front 10

Clinical
• Highly variable, depending on which and how many organs are involved.
• The kidneys, heart, skeletal muscles, skin and mesentery are most frequently involved, but lesions may also occur in any organ in the body.
• Constitutional symptoms such as fever and weight loss are common.

Back 10

Polyarteritis Nodosa (PAN)

Front 11

• Without tx, usually fatal, but corticosteroids and Cyclophosphamide therapy may lead to remission.

Back 11

Polyarteritis Nodosa (PAN)

Front 12

• It is today the most common form of vasculitis

Back 12

Temporal (Giant Cell) Arteritis

Front 13

• It can also involve additional cranial arteries, the aorta and its branches, and other arteries.
• The average age of onset is 70 years, and rarely occurs in those younger than 50.
• Women are affected slightly more often than men.

Back 13

Temporal (Giant Cell) Arteritis

Front 14

• The etiology of the disease is obscure. The occurrence of the disease in first-degree relatives supports a genetic component.
• The presence of activated CD4+ T-cells, suggests an immunological reaction, and a cell-mediated response to arterial antigens has been reported in some cases.

Back 14

Temporal (Giant Cell) Arteritis

Front 15

• Grossly, the affected vessel is cord-like and exhibits nodular thickening.
• The lumen is reduced to a slit or may be obliterated by a thrombus.
• Microscopic examination reveals a granulomatous inflammation of the media and intima, consisting of aggregates of macrophages, lymphocytes, and plasma cells with varying amounts of neuts and eosinophils.

Back 15

Temporal (Giant Cell) Arteritis

Front 16

Clinical
•Tends to be benign and self-limited, with the symptoms subsiding in 6-12 months.
•Patients present with H/A, and throbbing pain, sometimes along with malaise, fever, weight loss, and generalized muscular aching or stiffness in the shoulders and hips (polymyalgia rheumatica).
•Visual symptoms occur in almost 1/2 of the patients and may proceed from transient to permanent blindness
• The throbbing and pain is accompanied by swelling, tenderness, and redness in the skin overlying the vessel.

Back 16

Temporal (Giant Cell) Arteritis

Front 17

AKA Mucocutaneous Lymph Node Syndrome

Back 17

Kawasaki Disease

Front 18

•An acute, necrotizing vasculitis of infancy and early childhood characterized by:
high fever,
rash,
conjunctival and oral lesions,
lymphadenitis, and
desquamation of the fingertips, soles and palms.

Back 18

Kawasaki Disease

Front 19

• In 70% of the patients, the vasculitis affects the coronary arteries and leads to the formation of coronary artery aneurysms.
-Such lesions are the cause of death in 1-2% of the cases.

Back 19

Kawasaki Disease

Front 20

• The disease is usually self-limited, and although an infectious cause has been sought, none has been conclusively proved.
• Infection with Parvovirus B19 (slap-cheek syndrome) has been implicated in some cases, and there is evidence for various bacterial infections in others.

Back 20

Kawasaki Disease

Front 21

• An inflammatory disorder of large arteries, classically the aortic arch and its major branches.

Back 21

Takayasu Arteritis

Front 22

• Has a world-wide distribution and primarily affects young women (90%), the large majority of whom are younger than 30 years of age.
• The cause is unknown, but an autoimmune basis has been proposed.

Back 22

Takayasu Arteritis

Front 23

pulseless disease

Back 23

Takayasu Arteritis

•On gross examination, the aorta is thickened and the intima exhibits focal, raised plaques (all the way around).
•The branches of the aorta exhibit localized stenosis or occlusion, which interferes with blood flow and accounts for the synonym “Pulseless Disease” when the subclavian arteries are affected.
•The thoracic and abdominal aorta commonly show aneurysms.

Front 24

• Microscopically, there is a panarteritis, with infiltrates of neuts, lymphs, and giant cells (granulomatous inflammation).

Back 24

Takayasu Arteritis

Front 25

•Clinically, pt’s exhibit:
dizziness,
visual disturbances, and
occasionally symptoms early in the disease.

Back 25

Takayasu Arteritis

Front 26

• As the diseases progresses, cardiac symptoms appear with claudication of the arms and legs.
• Asymmetrical differences in the BP may occur, and the pulse in one extremity may be absent.
• The majority of patients eventually manifest CHF and visual defects, ranging from field defects to total blindness.
• Early disease responds to steroids, eventually though, lesions will require surgery.

Back 26

Takayasu Arteritis

Front 27

• A bastard!

Back 27

Wegener Granulomatosis

Front 28

• A systemic, necrotizing vasculitis of unknown etiology characterized by granulomatous lesions of the respiratory tract (the nose, sinuses, and the lungs) and renal glomerular disease.

Back 28

Wegener Granulomatosis

Front 29

• Men are affected more than women, usually in the 5th-6th decades of life.

Back 29

Wegener Granulomatosis

Front 30

• Over 90% of patients exhibit the C-ANCA in the blood.
Antibodies activate circulating neutrophils to attack the blood vessels.

Back 30

Wegener Granulomatosis

Front 31

• The lesions feature:
parenchymal necrosis,
vasculitis, and a
granulomatous inflammation composed of:
neuts, lymphs, plasma cells, macrophages, and eosinophils.
• The necrotizing granulomas in the lungs must be differentiated from those of T.B.

Back 31

Wegener Granulomatosis

Front 32

• Vasculitis involving the small arteries and veins may be found anywhere, but occur most frequently in the respiratory tract, kidney and spleen.
• (remember: upper and lower resp tract and kidneys)

Back 32

Wegener Granulomatosis

Front 33

• Characterized by acute inflammation, necrotizing granulomatous inflammation and fibrinoid necrosis, all leading to medial thickening, intimal proliferation and narrowing of the lumen.
• The most prominent pulmonary feature is a persistent bilateral pneumonia with nodular infiltrates that undergo cavitation (similar to tuberculosis).
-Chronic granulomatous sinusitis and ulcerations of the nasopharyngeal mucosa are common.

Back 33

Wegener Granulomatosis

Front 34

• The kidneys initially exhibit focal necrotizing glomerulonephritis, which progresses to:
Crescentic Glomerulonephritis (Rapidly Progressive Glomerulonephritis).

Back 34

Wegener Granulomatosis

Front 35

• Clinically, the large majority of patients presents with symptoms related to the respiratory tract, particularly pneumonia and sinusitis.
• The lungs are eventually involved in over 90% of cases.
On CXR, multiple cavitating pulmonary infiltrates are prominent.

Back 35

Wegener Granulomatosis

Front 36

• Hematuria and proteinuria are common and the glomerular disease may progress to acute renal failure (from the rapidly progressive GN).
• Rashes, muscular pains, joint involvement, and neurologic symptoms can occur.

Back 36

Wegener Granulomatosis

Front 37

• Untreated, most patients die within a year of onset (the mean survival is five months).
• Treatment with Cyclophosphamide produces a striking improvement, with both complete remissions and substantial disease-free intervals in most patients

Back 37

Wegener Granulomatosis

Front 38

• AKA Allergic granulomatosis and Angiitis.

Back 38

Churg-Strauss Syndrome

Front 39

• A systemic vasculitis with prominent eosinophilia that occurs in young people with asthma.

Back 39

Churg-Strauss Syndrome

Front 40

• Widespread necrotizing vascular lesions of the small and medium-sized arteries, arterioles, and veins of the lungs, spleen, kidney, heart, liver, and central nervous system.

Back 40

Churg-Strauss Syndrome

Front 41

• The lesions are characterized by granulomas with an intense eosinophilic infiltrate in and around blood vessels, resulting in fibrinoid necrosis and thrombosis.

Back 41

Churg-Strauss Syndrome

Front 42

• Both C-ANCA and P-ANCA is demonstrated in 2/3 of the patients.
• Untreated patients have a poor prognosis, but corticosteroids are successful.

Back 42

Churg-Strauss Syndrome

Front 43

• AKA Buerger Disease

Back 43

Thromboangiitis Obliterans

Front 44

• An occlusive, inflammatory disease of medium and small arteries in the distal arms and legs that occurs almost exclusively in middle-aged heavy smokers.
• The role of smoking is emphasized by the observation that cessation of smoking can be can be followed by remission, but the mechanism is unknown.
• Certain byproducts of tobacco elicit antibodies that can induce inflammation.

Back 44

Thromboangiitis Obliterans

Front 45

• There is a greater frequency in Japan, Israel, and India, suggesting possible predisposing genetic factors.

Back 45

Thromboangiitis Obliterans

Front 46

• The earliest changes is an acute inflammation of medium-sized and small arteries.
A neutrophilic infiltrate extends to involve neighboring veins and nerves.
• The involvement of the endothelium in the inflamed areas leads to thrombosis and obliteration of the lumen.
• Small microabscesses of the vessel wall, with neutrophils and giant cells are prominent.

Back 46

Thromboangiitis Obliterans

Front 47

• The early lesions can be severe enough to result in gangrene of the extremities, the only treatment being amputation.

Back 47

Thromboangiitis Obliterans

Front 48

•The symptoms usually start between the ages of 25 and 40 years.
The symptoms include claudacation (cramping pains in the muscles following exercise, which are quickly relieved by rest).
Patients often present with painful ulcerations of the digits, which can progress to the destruction of the tips of the involved digit.
•Those who continue to smoke may slowly lose both hands and feet.

Back 48

Thromboangiitis Obliterans

Front 49

a multi-factorial disease with a genetic and environmental component.
• They are more likely to occur in individuals from families known to have a connective tissue weakness, and family histories.

Back 49

Varicose Veins

Front 50

• Thrombotic occlusion of the veins (thrombo-phlebitis), prevents the outflow of venous blood, and also predisposes patients to varicosities.

Back 50

Varicose Veins