Blood Vessels Day 2 Flashcards
1
Q
Describe the six step pathogenesis of atherosclerosis
A
- Chronic endothelial injury (dysfunction)
- Accumulation of lipoproteins (mainly LDL) with subsequent oxidation
- Adhesion of monocytes with migration into the intima (now macrophages)
- Adhesion and activation of platelets
- Migration of smooth muscle cells becoming neointimal smooth muscle cells (proliferate and deposit extracellular matrix/collagen)
- Accumulation of lipids in macrophages (foam cells), smooth muscle cells and extracellular spaces
2
Q
What is an aneurysm?
A
•Localized abnormal dilation of a blood vessel or the wall of the heart
3
Q
The most important causes of aortic aneurysms are:
A
Atherosclerosis with associated inflammation (abdominal aorta)
- macrophage metalloproteinases and inflammation induced smooth muscle apoptosis weaken vessel wall
Hypertension via ischemic medial cystic degeneration (thoracic aorta)
4
Q
How can mycoses cause aneurysms?
A
•Mycotic aneurysms (infections)
- from embolization of a septic embolus (infective endocarditis)
- from extension of an adjacent suppurative process
- from circulating organisms infecting the arterial wall
5
Q
In addition to atherosclerosis, HTN, and mycoses, what are some other causes of aneursysms?
A
•Marfan syndrome (fibrillin),
Loeys-Dietz syndrome (TGF-β receptors),
Ehlers-Danlos syndrome (type III collagen),
scurvy (collagen x-linking),
trauma (traumatic aneurysms or arteriovenous aneurysms),
congenital defects (berry aneurysms),
syphilis and
vasculitides
6
Q
What is the difference between a true aneurysm and a false aneurysm?
A
true - bounded by arterial wall component or myocardium
false/pseudoaneurysm - transmural rupture creating hematoma, bound by extravascular CT
7
Q
What are the 2 appearances of true aneurysms?
A
- Saccular aneurysm – appears rounded
- Fusiform aneurysm – involves long segment of artery and is not rounded
8
Q
Where in the body do abdominal aortic aneurysms typically appear? How does this afect the sequelae? Who gets them?
A
Usually below the renal arteries
Renal complications with involvement of renal arteries
•M>F, smokers and age >50 years
9
Q
What are the causes of AAA?
A
- Inflammatory AAA (5-10%) - lymphocytes, plasma cells and macrophages +/- giant cells (uncertain cause and occur at younger age)
- IgG4 related disease with aortis and periaortitis - infiltrating IgG4+ plasma cells (may affect pancreas, biliary system, and salivary gland with fibrosis)
- Mycotic abdominal aortic aneurysms - atherosclerotic AAAs that have become infected (Salmonella gastroenteritis)
10
Q
How are thoracic aortic aneurysms similar to AAA?
A
Thoracic aortic aneurysms also occur with similar complications plus involvement of coronary ostia
11
Q
What are the clinical consequences of aortic aneurysm?
A
- Rupture into the peritoneum or retroperitoneal tissues (fatal in > 50%)
- Risk of rupture per year: size <4.0 cm (0%), 4.0-4.9 (1%); 5.0-5.9 (11%); >6.0 (25%) [usually repair >5 cm]
- Obstruction of a vessel leading to ischemic tissue injury
- Embolism from atheroma or mural thrombus
- Impingement on an adjacent structure, such as compression of a ureter or erosion of vertebrae
12
Q
How do AAAs typicall present?
A
•Presentation as an abdominal mass (often palpably pulsating) that simulates a tumor
13
Q
What do aneurysms and tertiary syphilis have in common?
A
•Obliterative endarteritis
in tertiary stage of syphilis (lues) involves vasa vasorum (arterioles) of the thoracic aorta
14
Q
What is syphilitic aortitis?
A
•Syphilitic aortitis
- obliterative endarteritis of vasa → ischemic injury of the media → loss of the medial elastic fibers and muscle cells
- Can lead to aneurysmal dilation that can include the aortic annulus leading to aortic valve incompetence
- Can involve coronary ostia
15
Q
What is “tree-barking” in regards to the aorta?
A
histological finding
contraction of fibrous scars with intervening segments of intima
16
Q
What is an aortic dissection?
A
Something typically repaired frantically by surgeons while anesthesiologists compare arm tans
Dissection of blood between planes of the media
Blood has entered (dissected) the wall of the vessel and separated the layers. Although this is shown as occurring through a tear in the lumen, dissections can also occur by rupture of the vessels of the vasa vasorum within the media.
17
Q
What patients is aortic dissection more common in? Does it always occur with aneurysm? What conditions predispose you towards it?
A
•May or may not occur with an aneurysm
•> 90% occur in men 40-60 with hypertension
•Arteriolosclerosis → smooth muscle cell loss
18
Q
What are some other conditions - other than arteriosclerosis - that predispose people towards aortic dissection?
A
- In younger people may be connective tissue disorder (Marfan, Ehlers-Danlos, Vit. C deficiency)
- Can be iatrogenic (arterial cannulation)
- Rarely occurs during or following pregnancy
- Occasionally 2ry to vasa vasorum rupture
19
Q
How is aortic dissection treated?
A
Antihypertensive therapy and aortic plication (65-75% survival)
20
Q
Can aortic dissection be a consequence of small vessel disease?
A
yes - vasa vasorum abruption into media tunica
21
Q
What is the clinical presentation of an aortic dissection?
A
•Sudden onset of excruciating pain, usually involves anterior chest, radiating to the back, and moving downward
22
Q
What is the most common COD with aortic dissection?
A
•Most common cause of death is rupture into the body cavities
23
Q
How many ways can an aorta dissect?
A
- Retrograde dissection into the aortic root → aortic valvular apparatus dysfunction with aortic insufficiency
- Can dissect into neck, coronary, renal, mesenteric, or iliac arteries, and compression of spinal arteries may cause transverse myelitis
- Occasionally the dissection can rupture back into vessel lumen causing a dual lumen vessel
24
Q
What can you do to potentially halt aortic dissection?
A
•Aggressive treatment of HTN may halt dissection
25
What is the classification scheme for aortic dissections? What is the worst classification?
Type A (proximal) involves the ascending aorta, either as part of a more extensive dissection (DeBakey I) or in isolation (DeBakey II).
Type B (distal or DeBakey III) dissections arise after the take-off of the great vessels.
Type A dissections typically have the most serious complications and greatest associated mortality.
26
Where along the aorta do aortic dissections arise?
Usually arise within 10 cm of aortic valve
27
What conditions is aortic dissection rarely comorbid with?
Dissection is unusual in substantial atherosclerosis or other cause of medial scarring such as syphilis
28
What are the genetics behind Marfan Syndrome?
**Loss of function mutation of fibrillin** (1 per 5,000)
* 75% of cases are familial (autosomal dominant pattern); rest are sporadic
* _Once incorrectly thought to be a dominant negative mutation!!!_
* Heterozygotes have clinical symptoms
* \> 500 mutations of **FBN1 gene** (15q21) for fibrillin 1
29
What is the pathology behind Marfan Syndrome?
**Loss of function mutation of fibrillin** (1 per 5,000)
Mutant fibrillin 1 prevents the assembly of normal microfibrils
With ↓fibrillin-1 there is **↑TGF-β activity and serum levels**
* Fibrillin 1 is involved in forming a complex that binds and inactivates TBF-β
* TGF-β involved in embryonic development, cell growth and apoptosis
* TGF-β ↑ collagen production and extracellular matrix (ECM) remodeling
* leads to overgrowth of bones and myxomatous changes in mitral valves
* Losartan (angiotensin II, type 1 receptor antagonist) for Rx?
30
How is Losartan helpful for Marfan's syndrome?
Losartan lowers BP, which will help control adverse outcome of aortic dissection
- will also reduce TGF-beta problem, whose activity is too high and causes too much growth
31
What is Loeys-Dietz syndrome, and why is it related to Marfan's?
Mutations in the TGF-β receptors give rise to a similar syndrome called **Loeys-Dietz syndrome** (Marfan syndrome, type II)
32
What are the principal clinical manifestations of Marfan Syndrome?
* Skeleton: Slender with abnormally long legs, arms, and fingers (arachnodactyly); high-arched palate; hyperextensibility of joints; spinal deformities (kyphoscoliosis); pectus excavatum or pigeon-breast
* Eyes: Bilateral dislocation (subluxation/**ectopia lentis**) of lens from weakness suspensory ligaments (ciliary zonules holding lens are made up exclusively of fibrillin)
* **Cardiovascular system: Aneurysmal dilation and aortic dissection**; dilation of the aortic valve ring (aortic incompetence); mitral and tricuspid valve floppy valve syndrome giving rise to congestive cardiac failure
* **Death from aortic rupture** is the most common cause of death
* Can occur at any age
* Cardiac failure also causes deaths
33
What is cystic medial degeneration?
Cross-section of aortic media from a patient with Marfan syndrome shows elastin fragmentation and areas devoid of elastin that resemble cystic spaces but are actually filled with proteoglycans (asterisks)
Normal media will have regular layered pattern of elastic tissue - when stained black, resembles wood grain
34
How is vasculitis typically separated, clinically and pathologically?
Large vessel vasculitis
- granulomatous disease
- giant cell arteritis, Takayasu arteritis
Medium Vessel Vasculitis
- imm complex mediated - polyarteritis nodosa
- antiendothelial cell Ab - Kowasaki disease
Small Vessel Vasculitis
- paucity of imm complexes - often with ANCA
- imm complex mediated
35
What are some important immune complex mediated pathogenesis of vasculitis?
Polyarteritis nodosa (HBsAg/HBsAg-Ab)
Drug-induced hypersensitivity reactions
_Antineutrophil cytoplasmic antibody (ANCA)-mediated (pauci-immune)_
Wegener granulomatosis - PR3-ANCA (c-ANCA)
Microscopic polyangiitis/polyarteritis
Churg-Strauss syndrome
_Direct antibody mediated_
Goodpasture syndrome (anti-glomerular basement membrane Ab)
Kawasaki disease (anti-endothelial Ab and also anti smooth muscle cell Ab)
36
What are some ANCA-mediated pathologies/causes for vasculitis? Which ANCA is each associated with?
PR3-ANCA (c-ANCA)
Wegener granulomatosis
MPO-ANCA (p-ANCA)
Microscopic polyangiitis/polyarteritis
Churg-Strauss syndrome
37
What can cause infectious vasculitis?
•Sometimes from direct invasion of bacteria (pseudomonas) or fungi (Aspergillus and mucormycosis)
* Can frequently accompany bacterial pneumonia
* Can occur adjacent to caseous tuberculous abscesses
* Can occur in superficial cerebral vessels in meningitis
* Can be secondary to septic emboli
- *Pseudomonas* and *Aspergillus* both thrive in vessel walls
38
What can result from an infectious vasculitis?
•May result in a mycotic aneurysm or induce thrombosis and infarction
39
How helpful are the associated symptoms of vasculitis in making a diagnosis? Why?
Vasculitis = Non-specific Constitutional Symptoms
•Fever
•Weight loss
•Myalgia
•Arthralgia
•Malaise
•Fatigue
Not specific enough to make a good Dx
40
What is Giant Cell/Temporal Arteritis?
Granulomatous arteritis of aorta, major branches and **often the temporal arteries** (can be tender on palpation)
41
What is the typical presentation of Giant Cell Arteritis?
**Usually \>50** and often **associated with polymyalgia rheumatica**
Most common vasculitis of elderly in US
People will present with headache, visual disturbance
- lumpy bumpy that hurt when palpated, d/t d/c vasculitis, lumpy areas are inflamed
The temporal artery of a patient with classic giant cell arteritis shows a thickened, nodular, and tender segment of a vessel on the surface of head (arrow).
42
What is the pathology behind Giant Cell/Temporal Arteritis?
Unknown mechanism, giant cells frequently involved
2/3 have anti-endothelial and/or anti-smooth muscle antibodies
43
What are some important associations with Temporal arteritis and other diseases/problems?
Ophthalmic arterial involvement →diplopia and permanent blindness
May cause giant cell aortitis and thoracic aortic aneurysm
Can involve coronary arteries
44
How should a clinician approach suspected Temporal Arteritis? How thoroughly should pathology examine an arterial specimen for this?
will cause blindness if untreated, medical emergency
Call surgeon who will take patient to surgery immediately
- get 3 cm of temporal aa, send to lab/pathology, get confirmation. Have to look for inflammation, then use elastic stain, if steroids used for too long then inflammation won’t be present. Examine until inflammation is found, inflammation pattern is intermittent.
- start high dose steroids to get inflammation down
45
What cellular changes will a pathologist appreciate with Temporal Arteritis?
Hematoxylin and eosin stain of section of temporal artery shows giant cells at the degenerated internal elastic lamina in active arteritis
Elastic tissue stain demonstrating focal destruction of internal elastic lamina and intimal thickening characteristic of long-standing or healed arteritis
46
What is Takayasu Arteritis?
Granulomatous inflammation of the aorta and its major branches.
47
You're on your third year rotations and got stuck with a first year resident on a night shift. The resident is assessing an older women who appears to not have a pulse. The resident then concludes the patient is a zombie and pulls out a gun to double-tap the pending epidemic. You are thinking more quickly, and give the resident an explanation of Takayasu Arteritis to save the patients life. What do you say?
Patients usually \<50 (females \< 40)
Thickening and narrowing of aortic arch and branches
Marked weakening of pulses (Pulseless Disease) and reduced blood pressures of upper extremities
48
Your resident is intrigued and asks you to explain associated problems of Takayasu arteritis. You say:
Ocular (retinal hemorrhages, blindness)
Neurologic
+/- Pulmonary (50%) (pulmonary HTN)
+/- Coronary arteries (myocardial infarcts)
+/- Renal (50%) arteries (renal HTN)
+/- Aortic valve insufficiency
49
What would you expect to see on angiogram, cross sections of carotid arteries, and histological appearance for Takayasu arteritis?
Aortic arch angiogram showing narrowing of brachiocephalic, carotid, and subclavian arteries
Gross photograph of two cross-sections of the right carotid artery taken at autopsy of the patient shown in A, demonstrating marked intimal thickening and adventitial fibrosis with minimal residual lumen.
Histologic appearance in active Takayasu aortitis, illustrating destruction and fibrosis of the arterial media associated with mononuclear infiltrates and inflammatory giant cells (arrows).
50
How are temporal and takayasu arteritis similar?
Similar presentation in both
- \<50 yo it's oft Takayasu, \>50 yo it's often Temporal
Treatment for both is high dose steroids
51
What is Kawasaki disease?
Arteritis involving large, medium-sized or small arteries
Usually self limited in children (80% \< 4 years)
52
What is the pathology behind Kawasaki disease?
Anti-endothelial cell and smooth muscle autoantibodies
53
What is the presentation of Kawasaki disease?
Main cause of acquired pediatric heart disease in North America and Japan (epidemic)
1% fatality rate
**Coronary arteries often involved +/- aneurysms**
Aorta and veins may be involved
+/- vascular aneurysms and thrombi
Associated with **mucocutaneous lymph node syndrome**
- acute usually self-limited disease with fever, conjunctival and oral erythema **(strawberry tongue)** and erosion, edema of the hands and feet, erythema of the palms and soles, a **desquamative skin rash** and enlargement of cervical lymph nodes
54
What is the treatment for Kawasaki disease?
Rx Immunomodulation (IV immunoglobulins) + anti- platelet agent (aspirin)
- high dose steroids
55
Is Kawasaki disease an infection?
Happens in young kids, present with what looks like an infection
- not an infection, despite constitutional symptoms
- hints include a skin rash on palms and soles, strawberry tongue
- order anti-endothelial cell Ab
- medical emergency, treat with high dose steroids right away
56
What is Buerger Disease?
Thromboangiitis Obliterans (Buerger Disease)
Segmental, thrombosing, acute and chronic inflammation of **medium-sized and small** **arteries** (tibial and radial), and extending to **veins and nerves** of the extremities
57
What is the clinical presentation for Buerger disease?
Previously occurred almost exclusively among heavy **cigarette-smoking** men, increasing in women
Begins before age 35 in most cases
Chronic ulcerations of the toes, feet, or fingers and gangrene
Secondary Raynaud phenomenon
Exercise induced instep claudication
Nodular phlebitis
Severe pain, even at rest (nerve involvement)
58
What is the pathology behind Buerger disease?
Massive reaction to tobacco antigens
Clinical presentation is often good enough to make a DX
Often involves entire neurovascular bundle
- often have claudification
Vessels are often thrombosed, end up with ulcers to skin
59
What is the treatment for Buerger disease?
Rx- stop smoking (during early disease)
60
What changes would you expect, histologically, for Buerger disease?
The lumen is occluded by a thrombus containing abscesses, and the vessel wall is infiltrated with leukocytes.
61
What is polyarteritis nodosa?
Polyarteritis nodosa (classic)
Necrotizing inflammation in **small to medium** arteries, arterioles, capillaries or venules
62
What is the clinical presentation of polyarteritis nodosa?
Usually of young adults
Malaise, fever, weight loss, HTN, abdominal pain and melena, muscular aches/pains, ulcers, infarcts, peripheral neuritis (mostly motor)
63
What is the pathology behind polyarteritis nodosa?
30% have hepatitis B surface Ag/Ab complexes
**segmental fibrinoid necrosis** and **thrombotic occlusion** of the lumen of this small artery. Note that part of the vessel wall at the upper right (arrow) is uninvolved.
Recurrent bouts possible, lesions can be of variable age
64
What should you associate with polyarteritis nodosa?
hepatitis B
65
What is Behcet's disease?
**Neutrophilic** vasculitis of **small to medium** arteries
66
What triad is the clinical presentation of Behcet's disease? What other systems can be involved?
**Triad**
* *1.recurrent oral aphthous ulcers
2. genital ulcers
3. uveitis**
Can also have GI, pulmonary and neurologic symptoms.
Can rupture aneurysms
67
What is useful for dx'ing Behcet's disease?
Can have positive pathergy test – minor trauma (sterile pinprick) causes exaggerated reaction
Also, Associated with HLA-B51
68
What is Wegener granulomatosis?
Granulomatosis with polyangiitis (Wegener granulomatosis)
- a small to medium vessel vasculitis
69
What is the triad for the disease for Wegener granulomatosis? Why is the triad important?
Triad –
1. Acute necrotizing granulomas of the upper and/or lower respiratory tract
2. Necrotizing or granulomatous vasculitis in the lungs and upper airways +/-other sites (eyes, skin, heart)
3. Renal disease with focal necrotizing glomerulonephritis (crescentic) with hematuria/proteinuria +/- renal failure
Triad is important for test questions, otherwise it's hard to distinguish it from Goodpasture's.
70
What is the pathological association you should make with Wegener granulomatosis?
**c-ANCA (PR3-ANCA)** - antineutrophil cytoplasmic autoantibodies targeting **proteinase 3 (PR3) in azurophilic granules** are highly specific
present in 95%
71
What does limited disease for Wegener's granulomatosis mean?
Limited disease means triad not entirely present
72
What is the clinical presentation of Wegener granulomatosis?
Clinical presentation
M \> F; ~40 years
Persistent pneumonitis; bilateral nodular and cavitary infiltrates in 95%
Chronic sinusitis in 90%
Mucosal ulcerations of the nasopharynx in 75%
Renal disease in 80%
Skin rashes
Muscle pains
Articular involvement
Mononeuritis or polyneuritis
Fever
73
How should Wegeners granulomatosis be treated? Can you leave it untreated?
Responds to immunosupression (steroids, chemo, and anti-TNF)
Always treat:
Untreated disease is malignant; 80% of patients die within 1 year
74
What is Churg-Strauss syndrome?
allergic granulomatosis and angiitis
75
What pathological associations should you make with Churg=Strauss syndrome?
**Eosinophil-rich and granulomatous necrotizing vasculitis**
Possible hyper-responsiveness to allergen
Strong association with allergic rhinitis, bronchial asthma, lung infiltrates
Blood eosinophilia
**p-ANCA (MPO-ANCA)** perinuclear **antimyeloperoxidase** in 50%
76
What are some clinical associations you can make with Churg-Strauss? Clinical presentation?
Palpable purpura
Involves respiratory tract
**Coronary arteritis and eosinophilic myocarditis are the principal causes of morbidity and mortality**
Severe renal disease is infrequent
77
What is microscopic polyangiitis?
leukocytoclastic vasculitis
Small Vessel Vasculitis
78
What is the pathology behind microscopic polyangiitis?
Necrotizing vasculitis with few or no immune deposits (pauci-immune) involving capillaries and small vessels. Can see fragmentation of neutrophils in and around blood vessel walls, with **all lesions of same age** in histological examination.
Possible reaction to drugs, organisms, or exogenous or tumor proteins
**p-ANCA (MPO-ANCA)** targeting perinuclear **antimyeloperoxidase** in lysosomes + in \>70%
79
What are some of the clinical presentation of microscopic polyangitis?
"**Palpable purpura**" of skin
**Necrotizing glomerulonephritis** (90% of patients)
**Pulmonary capillaritis** is common
**Hemoptysis**, arthralgia, abdominal pain or bleeding, hematuria, proteinuria, hemorrhage, and muscle pain or weakness
80
What are some other disorders associated with vasculitis?
Seen with rheumatoid arthritis, SLE, malignancy, mixed cryoglobulinemia and Henoch-Schönlein purpura
Vasculitis resembling hypersensitivity angiitis or classic polyarteritis nodosa
Rheumatoid vasculitis after long-standing, severe rheumatoid arthritis
visceral infarction
may cause a clinically significant aortitis
Lupus vasculitis
vs antiphospholipid antibody syndrome
aggressive anti-inflammatory therapy
vs aggressive anticoagulant therapy
81
