Cardio-Path-Vasculitis Flashcards
(127 cards)
1
Q
Which type of vessel only has endothelium, with no subendothelial layer or other tunics.
A
capillaries
2
Q
In arteries the intima includes a thin layer, the composed of elastin, with holes allowing better diffusion of substances from blood deeper into the wall.
A
internal elastic lamina
3
Q
Variable amounts of which 4 components are scattered throughout the muscle fibers of the tunica media and all of which are produced by the SMCs?
A
elastic fibers
and elastic lamellae,
reticular fibers, and
proteoglycans,
4
Q
general term for vessel wall inflammation?
A
vasculitis
5
Q
Concerning vasculitis,
Classification schemes attempt to group them according to vessel role of immune complexes, presence of specific autoantibodies, granuloma formation, organ , and population demographics.
A
diameter; specificity
6
Q
The granulomas of are found within the vessel wall as part of the inflammation comprising the vasculitis, but need not be present to render the diagnosis.
A
giant cell arteritis
7
Q
Not Giant cel arteritis, The granulomas of are larger, spanning between vessels, and associated with areas of tissue necrosis.
A
granulomatosis with polyangiitis
8
Q
Though the clinical manifestations are many, what do they largely depend on :
A
specific vascular bed that is affected
9
Q
Regarding vasculitis, besides findings referable to the affected tissue(s), there are usually also S and S of inflammation, eg, fever, myalgia, arthralgias, and malaise
A
systemic
10
Q
The 4 main immunologic mechanisms underlying noninfectious vasculitis are:
A
- Immune complex deposition
- Anti-neutrophil cytoplasmic antibodies (ANCAs)
- Anti-Endothelial Cell antibodies
- Autoreactive T cells
11
Q
Immune complex associated vasculitis is seen in immunologic disorders such as that are associated with autoantibody production
A
SLE
12
Q
Immune complexes involve both the antigen and :
A
antibody
13
Q
Many patients with vasculitis have circulating antibodies that react with neutrophil cytoplasmic antigens called:
A
“anti-neutrophil cytoplasmic antibodies (ANCAs).”
14
Q
What are a heterogeneous group of autoantibodies directed against constituents (mainly enzymes) of neutrophil primary granules, monocyte lysosomes, and ECs?
A
ANCAs
15
Q
What anti-neutrophil cytoplasmic Ab (ANCA) attacks PR3 is a neutrophil azurophilic granule constituent?
A
Anti-proteinase-3 (PR3-ANCA), previously called c-ANCA.
16
Q
Which type of vasculitis is associated with PR3-ANCAs?
A
granulomatosis with polyangiitis (WEGENERS)
17
Q
What is a lysosomal granule constituent involved in oxygen free radical generation.?
A
myeloperoxidase (MPO)
18
Q
Which ANCA is associated with microscopic polyangiitis and Churg-Strauss syndrome?
A
Anti-myeloperoxidase (MPO-ANCA), previously called p-ANCA.
19
Q
The close association between ANCA titers and disease activity suggests
a role for these antibodies
A
pathogenic
20
Q
ANCAs can directly/indirectly activate neutrophils, stimulating the release of reactive oxygen species and proteolytic enzymes; this may lead to EC injury associated with vasculitis.
A
directly
21
Q
In antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV), local infection, such as with Staphylococcus aureus, results in priming of via proinflammatory cytokines. This results in the surface expression of the ANCA antigens, allowing ANCAs to bind to and further activate that are rolling along the endothelium. Activation results in firm binding to the and release of lytic enzymes and reactive oxygen species (ROS), which damage the vessel wall
A
neutrophils; neutrophils; endothelium
22
Q
Antibodies to endothelial cells underlie certain vasculitides, for example in children:
A
Kawasaki disease (a medium vessel vasculitis)
23
Q
Autoreactive T cells cause injury in some forms of vasculitides characterized by formation of .
A
granulomas
24
Q
What is a chronic inflammatory disorder, typically with granulomatous inflammation, that principally affects large- to small-sized arteries in the head?
A
Giant cell (temporal) arteritis
25
How is the diagnosis for Giant cell (temporal) arteritis established?
biopsy of the temporal arteries.
26
As concerning biopsy of the temporal arteries, what are some other common affected arteries?
**Vertebral** and **ophthalmic arteries**, as well as the **aorta (giant cell aortitis)**
27
Because ophthalmic artery vasculitis can lead to sudden and permanent affected individuals must be promptly diagnosed and treated.
blindness,
28
What is the most common form of vasculitis among older adults in developed countries?
Giant cell (temporal) arteritis
29
Which vasculitis likely occurs as a result of a **T-cell–mediated immune response** to an as-yet uncharacterized vessel wall antigen.
• Pro-inflammatory cytokines (especially **TNF**) and **anti-EC antibodies** may also contribute.
Giant Cell Arteritis
30
Concerning giant cell arteritis, pathologic changes are not consistent throughout the affected vessel, these changes are considered .
patchy
31
In Giant cell arteritis, Involved arterial segments exhibit intimal thickening (and occasional thromboses) that reduce the vessel diameter and cause distal .
nodular; ischemia.
32
The vast majority of lesions in giant cell arteritis exhibit granulomatous inflammation within the inner centered on the internal elastic membrane; and of the internal elastic lamina as demonstrated in the slide.
media; fragmentation
33
What is being demonstrated in this slide of giant cell arteritis?
**Hematoxylin-eosin-stained** section of a temporal artery showing giant cells near the fragmented internal elastic membrane (arrow), along with medial and adventitial inflammation.
34
What is being demonstrated in this slide of giant cell arteritis?
Elastic tissue stain demonstrating focal destruction of internal elastic lamina (arrow) and intimal thickening (IT) characteristic of long-standing or healed arteritis.
35
• Temporal arteritis is **rare/common** before 50 years of age.
rare
36
Concerning giant cell arteritis, Other than Signs and symptoms that are vague and constitutional (eg, fever, fatigue, weight loss) what type of facial pain accompanies this disease:
most intense along the course of the superficial temporal artery, which is painful to palpation.
37
What 2 common occular symptoms (associated with involvement of the ophthalmic artery) abruptly appear in about 50% of patients with giant cell cell arteritis?
diplopia to complete vision loss.
38
What are 2 effective treatments for giant cell arteritis?
**Corticosteroid** or anti-**TNF therapies** are effective treatments.
39
In Giant cell arteritis, the superficial temporal artery is often , nodular and thickened
pulseless
40
Which vasculitis is a granulomatous vasculitis of medium- and large-sized arteries characterized principally by **ocular disturbances**, and **marked weakening of the pulses in the upper extremities** (hence the alternate name, “pulseless disease”)?
• Takayasu arteritis
41
What manifests with transmural scarring and thickening of the aorta - particularly the aortic arch and great vessels - with severe luminal narrowing of the major branch vessels as is demonstrated in the slides?
Takayasu Arteritis
42
What is the distinction between ginat cell arteritis and takayasu arteritis as they both share clinical and histologic features of giant cell aortitis?
basis of a **patient's age**; those older than 50 years of age are said to have giant cell aortitis, and lesions that occur in those younger than 50 years of age are designated Takayasu aortitis.
43
Takayasu arteritis classically affects the aortic and vessels.
arch; arch
44
Concerning takayasu arteritis, what other arteries, other than aortic arch and arch vessels are invovled in 50% of patients?
pulmonary arteries; renal and coronary arteries can also be affected
45
What explains upper-extremity weakness and faint carotid pulses in cases of takayasu arteritis?
The takeoffs of the great vessels can be markedly narrowed and even obliterated
46
There is a histologic spectrum ranging from adventitial **mononuclear infiltrates** and **perivascular cuffing** of the vasa vasorum, to intense **transmural mononuclear inflammation**, to **granulomatous inflammation**, including **giant cells and patchy medial necrosis.**
• Inflammation is associated with irregular of the vessel wall, intimal , and adventitial
thickening; hyperplasia; fibrosis.
47
Early signs and symptoms of takayasu arteritis are nonspecific, however, with progression, vascular signs and symptoms appear including r**educed upper-extremity blood pressure** and **pulse strength**; **neurologic deficits**; and **ocular disturbances**, including visual field defects, retinal hemorrhages, and total
blindness.
48
The evolution of Takayasu Arteritis is **fixed/variable?**
variable
49
In Takayasu arteritis, distal aorta disease can manifest as leg pain or :
claudication
50
In Takayasu arteritis, pulmonary artery involvement can cause pulmonary
hypertension
51
In 50% of patients with renal artery involvement with diagnosed Takayasu arteritis, can cause what systemic issue?
systemic hypertension
52
Which vasculitis is a systemic vasculitis of small - or medium - sized muscular arteries that typically involves the **renal and visceral vessels** and **spares the pulmonary circulation?**
Polyarteritis Nodosa (PAN)
53
One third of pts. with Polyarteritis Nodosa (PAN), have which type of chronic infection, which leads to the formation of immune complexes containing antigens that deposit in affected vessels.
**Hepatitis B infection,** and the Hep antigens are the antigens depositied in the affected vessels
54
Other than HEP B being the cause of a third of the cases of • Polyarteritis Nodosa (PAN), what is the cause in the remaining cases?
unknown
55
Which type of polyarteritis nodisa is a segmental transmural necrotizing inflammation of small-to medium-sized arteries, often with thrombosis?
Classic PAN
56
What are the 4 main visceral arteries affected in decreasing order of frequency?
Kidney,
heart,
liver,
gastrointestinal tract vessels
57
What are some of the effects of impaired perfusion related to polyarteritis nodosa?
ulcerations, infarcts, ischemic atrophy, or hemorrhages in the distribution of affected vessels
58
When the inflammatory process related to polyarteritis nodosa weakens the arterial wall, it can lead to which condition?
aneurysm and rupture
59
During which phase of polyarteritis nodosa, there is **transmural mixed inflammatory infiltrate** composed of **neutrophils** and **mononuclear cells**, frequently accompanied by fibrinoid necrosis and luminal thrombosis?
The acute phase
**Note:** the dark pink is fibrinoid necrosis and the black arrow demonstrates areas that are not involved
60
In polyarteritis nodosa, all stages of activity (from early to late) in different vessels or even within the same vessel
coexist
61
PAN is primarily a disease of adults, but can occur in all age groups.
young
62
The clinical course of PAN typically is **episodic/ persistent,** with long symptom-free intervals.
episodic
63
Why are the clinical manifestations of polyarteritis varied?
The systemic findings - malaise, fever, and weight loss - are nonspecific, and the **vascular involvement is widely scattered,**
64
Concerning PAN, what is the classic presentation involving the renal arteries?
rapidly accelerating hypertension
65
Concerning PAN, what is the classic presentation of GI arteries and lesions?
abdominal pain and bloody stools
66
Concerning PAN, what is the classic presentation when the motor nerves are affected?
diffuse muscular aches and pains; and peripheral neuritis,
67
Concerning PAN, which organ is often involved and is a majpr cause of death?
kidneys, renal involvement
68
How is renal involved PAN treated?
With **immunosuppression,** 5-year survival is close to 80%.\*
69
Which vasculitis is an acute, febrile, usually self-limited illness of infancy and childhood, associated with an arteritis of mainly large- to medium-sized vessels.?
Kawasaki disease
70
The clinical significance of Kawasaki disease stems from the involvement of which arteries?
coronary arteries
71
What is the clinical significance of the involvement of coronary arteries in Kawasaki disease?
Coronary arteritis can result in aneurysms that rupture or thrombose, causing myocardial infarction.
72
Concerning Kawasakin disease, most patients, approximately 80%, are under the age of:
4
73
In genetically susceptible individuals, a variety of infectious agents (mostly ) may trigger the disease.
viral
74
Which vasculitis results from a delayed-type hypersensitivity response directed against cross-reactive vascular antigen(s) that is usually a self-limited illness of infancy and childhood?
Kawasaki disease
75
Describe the process of delayed-type hypersensitivity response directed against cross-reactive vascular antigen(s) as it pertains to Kawasaki disease?
After infection (usually viral), subsequent **cytokine production and B cell activation** result in **auto-antibodies to endothelial cells (and SMC’s)** that precipitate the vasculitis.
76
What are the main clinical manifestations of Kawasaki disease?
conjunctival and oral erythema,
blistering,
edema of the hands and feet,
erythema of the palms and soles,
a desquamative rash,
and cervical lymph node enlargement.\*
77
Concerning Kawasaki dz, what are the cardiovascular sequelae that develop in 20% of patients?
asymptomatic **coronary arteritis**, to **coronary artery ectasia (dilation)**, to **large coronary artery aneurysms** (7-8 mm in diameter).
78
What is the treatement for Kawasaki disease?
intravenous immunoglobulin infusions (IVIG) **and** aspirin
Which decrease the incidence of symptomatic coronary artery disease
79
What is a necrotizing vasculitis that generally affects capillaries, as well as small arterioles and venules?
Microscopic polyangiitis (leukocytoclastic vasculitis)
80
Which 8 areas of the body can be inolved with Microscopic polyangiitis (leukocytoclastic vasculitis)?
skin,
mucous membranes,
lungs,
brain,
heart,
GI tract,
kidneys,
and muscle can be involved
81
90% of patients with Microscopic polyangiitis (leukocytoclastic vasculitis) develop :
Necrotizing glomerulonephritis.
82
Other than Necrotizing glomerulonephritis (90%), a common effect of Microscopic polyangiitis (leukocytoclastic vasculitis), what other effect is common?
pulmonary capillaritis
83
In some cases of microscopic polyangiitis, there are antibody responses to antigens, such as:
**drugs** (eg, penicillin), **microorganisms** (eg, streptococci), or **tumor proteins** have been implicated
84
Conceringin microscopic polyangiitis, , antibody responses to antigens such as drugs (eg, penicillin), microorganisms (eg, streptococci), or tumor protein reactions can lead to deposition or trigger secondary immune responses, eg, development of , that are pathogenic.
IC; ANCAs
85
Most cases of microscopic polyangiitis associated with autoantiody response are asociated with which type of ANCA?
MPO-ANCA (p-ANCA).
86
Like other diseases that involve ANCAs, microscopic polyangiitis works on Recruitment and activation of in the vascular beds is likely responsible for the disease manifestations
neutrophils
87
Describ the pathogenic process of ANCAs and neutrophils in a disease like microscopic polyangiitis?
In antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV), local infection, such as with Staphylococcus aureus, results in priming of neutrophils via proinflammatory cytokines. This results in the surface expression of the ANCA antigens, allowing ANCAs to bind to and further activate neutrophils that are rolling along the endothelium. Activation results in firm binding to the endothelium and release of lytic enzymes and reactive oxygen species (ROS), which damage the vessel wall.
88
Due to ANCA activation of more neutrophils and generation of ROS species, what is another manner by which ANCA activated neutrophils can damage the vessel wall in vasculitis?
Also, the alternative pathway of complement is activated with generation of the powerful neutrophil **chemoattractant C5a.** This amplification loop contributes to the necrotizing inflammation of the vessel wall.
89
In microscopic polyangiitis, histologically, segmental fibrinoid of the media with focal necrotizing lesions are seen.
necrosis; transmural
**Note:** In some areas, only infiltrating neutrophils undergoing fragmentation are seen, giving rise to the term leukocytoclastic vasculitis (microscopic polyangiitis)
neutrophil fragements are seen in this image
90
Concerning microscopic polyangiitis, if the renal vascular bed is involved, what signs and symptoms can be seen?
hemoptysis, hematuria, proteinuria,
91
Concerning microscopic polyangiitis, if the gi vascular bed is involved, what signs and symptoms can be seen?
abdominal pain or bleeding
92
Microscopic polyangiitis can lead to muscle pain or weakness, and palpable cutaneous , if it involves vascular beds in the muscles and skin.
purpura.
93
What two methods of treatement can cause microcsopic polyangiitis to induce remission, With the exception of patients with widespread renal or CNS involvement?
immunosuppression and removal of the offending agent
94
Granulomatosis with Polyangiitis (GPA) was previously called
Wegener granulomatosis
95
Which vasculitis is characterized by a triad of:
**Necrotizing granulomas** of the **upper-respiratory tract, the lower-respiratory tract or both. •**
**Necrotizing or granulomatous vasculitis** affecting small- to medium- sized vessels, most prominently the **lungs and upper airways**, but other sites as well.
• Focal **necrotizing**, often **crescentic**, **glomerulonephritis.\***
Granulomatosis with Polyangiitis (GPA)
96
Conversely, when widespread the disease may affect the **eyes, skin,** and other **organs**, most notably the **heart;** clinically, widespread GPA resembles PAN with the additional feature of involvement.
respiratory
97
Granulomatosis With PolyangiitisIt is likely initiated as a **cell-mediated hypersensitivity** response to infectious or environmental AGs.
inhaled
98
Which ANCA represents is involved with Granulomatosis With Polyangiitis, and is involved with 95% of cases?
PR3-ANCAs (c-ANCAs)
99
What is a useful marker for disease activity in Granulomatosis With Polyangiitis?
PR3-ANCAs (c-ANCAs
100
Examples of Granulomatosis With Polyangiitis in the upper respiratory tract can also be called granulomatous . There can also be ulcerative lesions of the nose, palate, or pharynx.
sinusitis
note: A. GAP inflammation B. necrosis C. giant cells with granulomas D. vasculitis
101
What is the tissue invovled with this case of Granulomatosis With Polyangiitis:
Lung findings range from diffuse parenchymal infiltrates to granulomatous nodules.
note: notice cavity (black star) due to necrosis
102
There is **multifocal necrotizing granulomatous vasculitis** with a surrounding **fibroblastic proliferation.**
**note:** notice the giant cells
103
Describe this example of Granulomatosis With Polyangiitis
Multiple granulomata can coalesce to produce radiographically visible nodules with central cavitation
104
WIth the respiratory involvement of Granulomatosis With Polyangiitis, descruction of vessels can lead to hemorrhage and bloody sputum called .
hemoptysis
105
What is being demonstrated in this slide in this case of Granulomatosis With Polyangiitis
Focal and segmental glomerulosclerosis (periodic acid–Schiff stain), seen as a collection of scarred, obliterated capillaries and accumulations of matrix material in part of the affected glomerulus
-can lead to thrombosis
106
What is being demonstrated in this slide in this case of Granulomatosis With Polyangiitis:
Crescentic glomerulonephritis (silver stain). Arrows indicate areas of necrosis and crescent formation. The segmental distribution in this case is typical of ANCA (anti-neutrophil cytoplasmic antibody)–associated crescentic glomerulonephritis.
107
What is causing the cresent shape cells in this case of Granulomatosis With Polyangiitis
parietal cell proliferation forming epithelial crescents (crescentic glomerulonephritis).
108
Who is the typical patient with Granulomatosis With Polyangiitis
middle aged man
109
Classic presentatikons with Granulomatosis With Polyangiitis include (4):
bilateral pneumonitis with nodules and cavitary lesions (95%),
chronic sinusitis (90%),
mucosal ulcerations of the nasopharynx (75%),
and renal disease (80%)
110
What are some more mild common symptoms that can also occur with Granulomatosis With Polyangiitis:
\* Rash, myalgias, articular involvement, neuritis, and fever also may occur.
111
Concerning Granulomatosis With Polyangiitis: what is the mortality rate at one year
80%
112
What are the 4 treatments that have provent the outcome of Granulomatosis With Polyangiitis considerably:
steroids,
cyclophosphamide,
TNF inhibitors, and
anti-B-cell antibodies (rituximab)
113
Of those that survive Granulomatosis With Polyangiitis, there is a high risk for relapses that may ultimately lead to what type of organ failure?
renal failure
114
What vasculitis is a **small-vessel necrotizing vasculitis** classically associated with asthma, allergic rhinitis, lung infiltrates, peripheral eosinophilia, extravascular necrotizing granulomas, and infiltration of vessels and perivascular tissues by **eosinophils**
Churg-Strauss syndrome (allergic granulomatosis and angiitis)
115
Churg-Strauss syndrome is a **rare/common** disorder with major associations with with Cutaneous involvement (with palpable purpura), gastrointestinal bleeding, and disease
rare; renal
116
In regards to Churg-Strauss Syndrome (allergic granulomatosis and Cytotoxicity produced by the myocardial eosinophilic infiltrates often leads:
cardiomyopathy. (restrictive)
117
Which vasculitis is characterized by segmental, thrombosing, acute and chronic inflammation of **medium - and small - sized arteries**, principally the **tibial and radial** arteries, with occasional secondary extension into the veins and nerves of the extremities?
Thromboangiitis Obliterans (Buerger Disease)
118
Which vasculitis occurs almost exclusively in **heavy tobacco smokers**, and usually develops **before 35 years of age**
Thromboangiitis Obliterans (Buerger Disease)
119
Which vasculitis has **genetic predilection** is suggested by an increased prevalence in **certain ethnic groups (Israeli, Indian subcontinent, Japanese**), and an association with certain **HLA haplotypes?**
Thromboangiitis obliterans (Buerger disease)
120
Morphologicaly, Thromboangiitis obliterans (Buerger disease), has sharply segmental and transmural vasculitis of medium- and small-sized arteries, predominantly those of the _u._
acute; chronic; extremities
121
In the early stages of Thromboangiitis Obliterans, mixed inflammatory infiltrates are accompanied by thrombosis as is demonstrated in the slide.
Thromboangiitis Obliterans
note: luminal thrombosis with transmural inflammation (leukocytes infiltrates)
122
Clinical features of which vasculitis include cold-induced Raynaud phenomenon, instep foot pain induced by exercise (instep claudication), and superficial nodular phlebitis?
Thromboangiitis Obliterans (Buerger Disease)
123
With vascular insufficiency, such as in the case of Thromboangiitis Obliterans (Buerger Disease), it can lead to severe , even at rest
pain (from neural involvement)
124
Concerning Thromboangiitis Obliterans, Chronic extremity ulcerations may develop, progressing over time to
gangrene
125
What can prevent further attacks of vascular insufficiency and pain caused by Thromboangiitis Obliterans?
Smoking abstinence, however, the vascular lesions do not respond to smoking abstinence.
126
What is the difference in location of the granulomas found in giant cell arteritis vs. granulomatosis with polyangiitis?
granulomas of giant cell arteritis are found within the vessel wall while granulomas of granulomatosis with polyangiitis are larger, spanning between vessels, and associated with areas of tissue necrosis.
127
