04.06 and 04.07 - Vascular Disease, Aneurysms, Dissections, Vasculitis, etc. Flashcards Preview

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What is another use of the term ectasia?

- Also used for dilatations of tubular structures besides blood vessels that are discrete and localized

- REMEMBER: in terms of vasculature, an ectasia is a dilatation that is NOT discrete or localized (which would be an aneurysm)  



Is aortic dissection always associated with radiologically detectable aortic dilation?



What is vasculitis? What are its signs and symptoms?

- Heterogeneous group of diseases: mostly auto-immune, mostly treatable, but some life-threatening

- Signs and symptoms: NON-SPECIFIC (biopsy dx)

1. Fever, myalgias, arthralgias, malaise, palpable purpura, focal skin necrosis, ulceration, livedo reticularis, urticaria, myositis

3. Peripheral neuropathy, GI ulcers, perforation, intussusception (telescoping gut), pancreatitis, hemoptysis, pulmonary infiltrates, hematuria, proteinuria, organ ischemia, infarction, etc.


What is the most essential element for diagnosis of vasculitis?


- Distribution of organ involvement and biopsy also key to specific diagnosis 


What is the major division of vasculitis? What are some infectious causes? Major complication?

- Infectious vs. non-infectious (primary) 

- Infectious causes: 1) fungal (esp aspergillus), 2) bac (e.g. pseudomonas), 3) viral (esp cytomegalovirus)

- May cause a “mycotic” aneurysm (misnomer because it is not necessarily due to a fungus, actually is rarely due to a fungus)


How is primary vasculitis classified?

By the size of the blood vessels inflamed


What are the signs and symptoms of temporal arteritis?

- Common, typically in elderly, white, N European F

- Dreaded complication: blindness 

- Signs and symptoms:

1. Headache (75% of patients)

2. Swollen tender artery (50%)

3. Scalp tenderness (50%)

4. Visual disturbances (50%)

5. Jaw claudication (50%)

6. Fever (25%), malaise, weight loss


What is the pathology of temporal giant cell arteritis?

- Inflammation

1. Segmental

2. Transmural

3. Granulomatous w/multinucleated giant cells centering on (destroying) internal elastic lamina

- + lymphocytes, intimal thickening, cell proliferation, luminal stenosis


What is the arrow pointing at?

- Transmural arteritis narrowing lumen, with a prominent granuloma 


What are these arrows pointing at?

- Giant cells eating internal elastic lamina 

- Residual lamina (left) black on elastin stain 


Briefly, what is the pathogenesis of giant cell arteritis?

- Multinucleated giant cell attack on calcified internal elastic lamina in arteries and calcified atrophic tunica media of thoracic aorta

- Prerequisite for arterial calcification explains why giant cell arteritis occurs almost exclusively in the elderly 

- Both the innate and adaptive arms of the immune system lead to vessel injury through distinct pathways

- Prompt treatment important (to prevent blindness): high dose corticosteroid therapy 


How are dendritic cells involved in the patho of temporal giant cell arteritis?

- Dendritic cells initiate immune response; normally, immune cells in arteries mostly immature dendritic cells w/characteristically high threshold of activation 

1. Do NOT express co-stimulatory molecules, i.e., CD80, 86; anergic tolerogenic state for T cells.

- Ags (from pathogens or formed by calcification) activate immature dendritic cells that produce large amounts of IL-12 and IL-18, up-regulate release of IFN-gamma from T cells, release chemokines CCL19 and CCL21, which bind CCR7, resulting in local arrest of activated dendritic cells, trapped in the arterial wall

- Activation of vascular dendritic cells mediated via ligation of TLRs: PAMP, DAMP -> activation of IC TRAM motif, IC 2nd message, activation of NfKB, which enters nucleus and induces translation of genes for pro-inflammatory molecules

- Distribution of TLRs in vessel wall by embryological origin: aortic arch and its branches from ectoderm, descending aorta from mesoderm; TLR-4 abundantly expressed on adventitial dendritic cells

- IFN-gamma produced in lg amts leads to mono-nuclear infiltration, and activated dendritic cells secrete pro-inflammatory cytokines, mainly IL-2, IL-6 and IFN-gamma, which, recruit inflammatory cells, inhibit cell migration, enhance T cell proliferation, and stimulate T and B cells -> result is amplification of the immune response, through positive feedback loops 

- Progression of immune response depends on Th1 and Th17 CD4 T cells from two distinct immune axes: an IL-12-IFN-gamma axis and an IL-1-IL-23 axis


How are TH1 cells and IFN-gamma implicated in temporal giant cell arteritis?

- TH1 cells: dominant cell pop in intramural lesions and periphery of pts with untreated giant cell arteritis 

- Produce IFN-gamma; steroid therapy cannot affect expansion of this subpop bc continuous signaling from dendritic cells that continue to release IL-12

- INC IFN-gamma -> production of VEGF and PDGF, implicated in intimal response and lumen stenosis

1. VEGF may promote IFN-gamma production, so cycle of inflammation and stenosing fibrosis

- Untreated pts: number of Th17 cells elevated 10x in peripheral blood; accumulate in vascular infiltrates

- Prednisone leads to almost complete reduction of circulating, lesional Th17 -> systemic manifestations of giant cell arteritis most responsive to this, and coincide w/normalization of Th17 cell levels and suppression of IL-1 – IL-6 – IL-17 axis

- IFN-gamma induces macros to form multinucleated giant cells and granulomas; pro-inflammatory envo, (IL-1, IL-6, IL-17, IL-23, IFN-gamma) promotes infiltration of arterial wall by activated monocytes

- Matrix metalloproteases released by macros and smooth muscle cells assoc w/matrix degeneration, intimal hyperplasia and luminal narrowing; MMP-2MMP-9 destroy elastin and play primary role in the internal elastic lamina degradation 


What is Takayasu arteritis?

- Rare; typically young, east Asian females 

- Clinical manifestations:

1. Loss of arm pulses (pulseless disease), intermittent arm claudication, skin ulcers

2. Fever, fatigue, weight loss, HTN (reno-vascular), angina pectoris, headaches, seizures

3. Nausea, vomiting, arthritis or arthralgias


What is the pathology of Takayasu arteritis?

- Inflammation

1. Segmental

2. Transmural

3. Necrotizing

4. Loosely granulomatous w/multinucleated giant cells

- + lymphocytes, intimal and adventitial thickening, medial loss of elastic fibers, thinning, luminal stenosis


What might this be?

- Takayasu arteritis w/intimal tear, dissection, rupture, hemopericardium

- Caused cardiac tamponade and sudden death


What do you see here?

- Loose, granulomatous inflammation 

- Macros and multinucleated giant cells 


How do you diagnose and treat Takayasu arteritis? What is the prognosis?

- Diagnosis: 3 or more of the following

1. Age <40

2. Limb claudication

3. Decreased brachial pulse

4. Unequal arm blood pressures

5. Subclavian or aortic bruit

6. Stenosis of aorta or major branches on angiogram 

Treatment: corticosteroids and cytotoxic immuno-suppressive therapy 

Prognosis: not good 


What is polyarteritis nodosa? Clinical manifestations?

- Uncommon; typically white males in their 40's

- Clinical manifestations:

1. Neuropathy (78%, sensory or motor, e.g., wrist, foot drop)

2. Renal failure (w/HTN)

3. Fever, fatigue, weight loss

4. Acute abdomen, cholecystitis, pancreatitis

5. Angina pectoris, livedo reticularis



What is this?

- Livedo reticularis 

- Caused by polyarteritis nodosa, but not specific for it


What is the pathology of polyarteritis nodosa?

- Segmental + transmural + nodular arteritis with fibrinoid necrosis (perhaps most characteristic feature), neutrophils (acute phase), intimal thickening, cell proliferation and degeneration, luminal stenosis

- +/- thrombosis, +/- occlusion, +/- rupture, all esp at branchpoints

- Later: chronic inflammation, fibroblasts, and scarring +/- aneurysms

- Typically with lesions at different phases


Why do pts with polyarteritis nodosa usually have lesions at different phases at the same time?

- Patients typically present only after having the disease for months, sometimes years

- Waxing and waning partial remissions and relapses producing crops of lesions, some new at the time of diagnosis and some old at the time of diagnosis


What do you see here?

- Polyarteritis nodosa in acute phase

- Fibrinoid necrosis and neutrophilic infiltration (ants crawling all over it)


What is this?

- Severe, necrotizing arteritis at edge of involved segment of an artery 


What do you see here?

- Transmural arteritis with fibrinoid necrosis highlighted by trichrome stain 


What are the dx Abs, tx, and prognosis for polyarteritis nodosa?

- NO diagnostic antibodies (ANCA-negative!!)

- Tx: corticosteroids (+ cytotoxic immunosuppressive, if severe)

- Prognosis: improves from 13% untreated to 80% treated, making this a DON’T MISS THIS ONE dx


What is Kawasaki disease? How do you dx it?

- Aka, mucocutaneous lymph node syndrome 

- Rare; typically east Asians around 1 y/o 

- Aneurysms characteristic of this disease 

- NO blood test -> clinical diagnosis based on history and physical exam

- About 20% of untreated pts devo CV sequelae, ranging from asymptomatic coronary arteritis, to coronary artery ectasia, to giant coronary artery aneurysms (7 to 8 mm) -> may lead to rupture, thrombosis, MI, and sudden death


What are the diagnostic features of Kawasaki disease?

- Requires fever for 5 or more days, plus 4 of the following:

1) Polymorphous rash

2) Bilateral conjunctival injection

3) Cervical lymphadenopathy

4) Extremity changes: erythema of palms/soles, indurative edema of hands/feet, membranous desquamation of fingertips, Beau’s lines (transverse grooves of the nails)

5) Mucous membrane changes: diffuse injection of oral and pharyngeal mucosa, erythema or fissuring of tongue, strawberry tongue


What do you see here?

Polymorphous rash and strawberry tongue of Kawasaki's disease


What do you think is going on here?

- Diffuse enlargement of right coronary (top) & left anterior descending artery (bottom) with large aneurysm of right coronary (mid left)

- Kawasaki disease: 18 month old boy sick for 2 wks