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

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Flashcards in 04.06 and 04.07 - Vascular Disease, Aneurysms, Dissections, Vasculitis, etc. Deck (83):

What are the 5 main components of arteries that we should be aware of?

- Tunica intima: inner layer (lining)

- Tunica media: middle layer (smooth muscle)

- Tunica adventitia: outer layer 

- Internal elastic lamina: mem separating intima and media

- Vasa vasorum: small blood vessels in tunica media and adventitia of arteries so large that oxygen and nutrients can't reach these layers by diffusion from lumen


What are 3 important types of arteries?

Elastic: largest aa (aorta, innominate/braciocephalic, subclavian, common carotid, iliac, pulmonary)  

Muscular: medium size aa (>0.2cm in diameter), incl coronary cerebral, renal, hepatic, femoral, popliteal 

Arterioles: smallest aa (20-100 microns in diameter)


What is an arteriovenous fistula?

Direct connections between aa and vv bypassing intervening capillary bed


What is fibromuscular dysplasia?

- Focal, irregular arterial wall thickening with intimal and medial hyperplasia and fibrosis leading to luminal stenosis (narrowing)

- Presumptively due to developmental disordered growth (NOT pre neoplastic!!)

- Typically in renal, carotid, splanchnic or vertebral aa

- Most commonly diagnosed in young women


What are hyperplastic and hyaline arteriolosclerosis?

- Hyperplastic: concentric wall thickening due to smooth muscle cell hyperplasia and hypertrophy, and thickened reduplicated basement membrane (caused by HTN and causes luminal narrowing; can resemble onion skin) 

- Hyaline: wall thickening due to leakage of plasma protein into wall and increased secretion of matrix by smooth muscle cells (caused by HTN) 

1. Differential diagnosis: amyloidosis or fibrinoid change/necrosis 


What are fibrinoid change and medial calcific sclerosis?

- Fibrinoid change/necrosis: leakage of plasma protein into wall +/- necrosis (caused by malignant hypertension or vasculitis)

- Medial calcific sclerosis: degenerative calcification of internal elastic lamina, spreading into tunica media, not thought to be clinically significant by itself


What do you see here? What might have cause this?

- Onion-skin appearance of arteriole with hyperplastic arteriolosclerosis likely due to HTN

- Scleroderma causes similar onion-skin thickening, but of larger, interlobar renal arteries 

- Fibromuscular dysplasia causes similar causes similar thickening, but of larger renal arteries outside the renal parenchyma


What do you see here? What are some likely causes?

- Smooth homogenous thickening of an arteriole with hyaline arteriolosclerosis likely due to HTN 

- Amyloidosis causes similar appearance, but not limited to arterioles 

- Fibrinoid change/necrosis has similar appearance, but often part of vasculitis 


What do you see here?

Fibrinoid change


What do you see here?

- Fibrinoid necrosis 

- Due to polyarteritis nodosa; not all the vasculitis and surrounding inflammation


What do you see here?

Medial calcific sclerosis (may play a role in devo of temporal giant cell arteritis)


What is this?

- Medial calcific sclerosis 

- With intimal thickening, presumably due to separate atherosclerosis, since medial calcific sclerosis occurs in old people, who always also have atherosclerosis 


What is an aneurysm?

Discrete, localized dilatation (outpouching) of blood vessel or heart


What is a dissection?

Tear of the tunica intima, letting luminal blood under high pressure into the tunica media, where it tunnels (dissects) a second lumen


What is an ectasia?

Non-discrete, non-localized dilatation, often torturous, of blood vessel or duct 


What is Marfan syndrome?

- FBN1 gene for fibrillin-1; auto dom; 1 in 5000

- Abnormal fibrillin & excessive activation of TGF-beta bc normal microfibrils sequester TGF-beta

- Causes cystic medionecrosis of ascending aorta, leading to dilation, predisposing to aortic dissection (cause of death in up to 45% of cases); tall body 

- Mainstay of treatment = administration of beta-blockers (which reduce HR, BP and aortic wall stress); angiotensin-2 receptor blockade promising new tx

Fibrillin: EC glycoproteins responsible for structuring elastin fibers 


What is Ehlers-Danlos syndrome?

- Clinically and genetically heterogeneous group of inherited disorders due to defects in synthesis or structure of fibrillar collagen 

- Vascular types involve COL3A1 gene for type III collagen

1. Usually auto dom, and have spontaneous rupture of blood vessels and intestines bc rich in type III collagen


What are cystic medial degeneration and vasculitis?

Cystic medial degeneration: loss of smooth muscle cells and elastic fibers in tunica media of large arteries 

Vasculitis: inflammation of blood vessels


What are the epi, patho, and causes of aortic aneurysms?

- Epi: common, esp in elderly, white M; run in families

1. Associated w/smoking, HTN, hyperlipidemia

- Patho: interplay b/t atherosclerosis & genetically determined degeneration of tunica media

1. Increased matrix metalloproteinases +/- DEC tissue inhibitors of them

2. Spillover inflammation from atherosclerosis

- Less common causes

1. Genetic defects in fibrillin or collagen (Marfan)

2. Infection (called mycotic, even when not fungal, which is most of the time)

3. Vasculitis (autoimmune, e.g. giant cell arteritis)


What is this?

- Aortic aneurysm from superior mesenteric artery (bottom) to bifurcation (top)

- Cut edge of aorta: black line = normal circumference 

- Variegated brown, mural thrombus 

- More common in the abdomen (75%), and thrombus usually forms in it


What is the arrow pointing to?

- Cystic medial degeneration in tunica media (used to be called necrosis) = loss of smooth muscle cells and elastic fibers, leaving cystic areas of myxoid matrix 

- Common in aortic aneurysm 


What is the difference between left and right?

- Left: elastic stain of aortic tunica media at edge of area of cystic medial degeneration 

- Right: elastic stain of aortic tunica media in area with normal elastic fiber density 


What are the symptoms, signs, diagnosis, and treatment for aortic aneurysms?

- Symptoms: usually none, but may cause back pain (especially if leaking)

- Signs: usually none

- Diagnosis: imaging

- Treatment: stenting or open repair


What are some complications of aortic aneurysm?

- Rupture: major determinant = diameter

- Mural thrombus formation 

- Embolism of atheroma or thrombus

- Obstruction of aortic branches

- Aortoenteric fistula


What is the epi and patho of an aortic dissection? What are the types?

- Catastrophic tear of tunica intima; high pressure luminal blood in tunica media, tunnels 2nd lumen

- Epi: Uncommon (2000/yr in US), but most common in late middle age (black M) 

Patho: intimal tear; rarely obvious what caused it

1. Medial dissection: comm assoc w/cystic medial degeneration

- Type A: ascending aorta +/- more, more common & serious

- Type B:  involves descending aorta alone


What are the treatments/survival rates for the two types of aortic dissections?

- Type A: rapid dx; begin intensive anti-HTN therapy and surgical plication of aortic intimal tear

1. Can save 65% to 85% of pts 

- Type B: most can be managed conservatively

1. 75% survival rate whether treated w/sx or with anti-HTN meds only


What do you see here?

Aortic dissection (false lumen above)


What are the symptoms and complications of aortic dissections?

- Symptoms: sudden severe sharp “tearing” chest pain, anterior (type A) or between scapulae (type B), moving as dissection progresses

1. +/- arm pain & weakness (subclavian), altered mental status (carotid), or collapse (rupture) 

- Complications: occlusion of aortic branches

1. Rupture, commonly into pericardium, less often into left pleural cavity


What is going on here?

Rupture of aortic dissection into chest (probe is in the intimal tear)


How do you diagnose and treat aortic dissection?

- Diagnosis: transesophageal echocardiogram, CT, or MRI

- Treatment: reduce blood pressure to low normal or surgery (primarily for type A)


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


What is this?

Aneurysm cut open showing thrombus


What is the pathology of Kawasaki disease?

Endo necrosis + transmural inflammation with neutros, lymphos wall necrosis, aneurysms, and thrombosis


What do you see on the left and right?

- Left: interface of arterial intima and thrombosis

- Right: mixed acute and chronic arteritis


How do you treat Kawasaki disease? What is the prognosis?

- Treatment: aspirin and IVIg 

1. ASA risks Reye syndrome, but Kawasaki tips risk/benefit ratio in favor of giving it

- Prognosis: good (majority of aneurysms resolve); reduces risk of symptomatic coronary artery disease

- NOTE: Reye's rare but serious condition that causes swelling in liver and brain -> most often kids, teens recovering from viral infection like flu or chickenpox. Signs, symptoms of confusion, seizures, LOC need emergency tx -> early dx, tx can be lifesaving 


What is microscopic polyangiitis? What are its major clinical features?

- Aka, hypersensitivity or leukocytoclastic vasculitis: a necrotizing vasculitis that generally affects capillaries, small arterioles, and venules 

- All lesions tend to be of same age in pt

- Skin, mucous membranes, lungs, brain, heart, gut, kidneys, and muscle can all be involved

- Necrotizing glomerulonephritis (90% of pts) and pulmonary capillaritis are common

- Major clinical features: hemoptysis, hematuria, and proteinuria, bowel pain or bleeding, muscle pain or weakness, and palpable purpura

1. Except in those w/widespread renal or brain involvement, immunosuppression induces remission, markedly improves long-term survival


What is the pathogenesis of microscopic polyangiitis?

- Ab responses to Ags like drugs (penicillin), micro-organisms (streptococci), heterologous proteins, or tumor proteins -> can lead to immune complex depo or secondary immune responses (e.g., anti-neutrophil cytoplasmic antibodies, ANCAs) that are pathogenic 

- Most assoc w/anti-myeloperoxidase, MPO-ANCA (perinuclear, or P-ANCA)

- Recruitment, activation of neutros in vascular beds responsible for disease manifestations

- Segmental fibrinoid necrosis and in some areas (typically postcapillary venules), only infiltrating neutrophils, many undergoing apoptosis, are seen

- While Ig's, complement components can be in early skin lesions, little or no Ig's found in most lesions

1. Pauci-immune injury: vasculitis with minimal evidence of hypersensitivity on immuno-fluorescence and lack of Anti-glomerular BM Ab


What is granulomatosis with polyangiitis (Wegener's)?

- Uncommon, but typically whites in 40's 

- Necrotizing granulomatous vasculitis of both aa and vv in upper and lower respiratory tracts, kidneys 

- Geographic areas of necrosis with basophilic debris and palisaded histiocytes around them (like rheumatoid nodules -> see front of card) 

- 95% have anti-neutrophil cytoplasmic auto-Abs for proteinase-3 (ANCA-PR3; diffuse cytoplasmic, C-ANCA)


What is going on here?

- Mucosal ulcers 

- Necrotizing lesions 

- Can be destructive of nasal cartilage, leading to saddle nose deformity 

- Characteristic of: granulomatosis with polyangiitis 


What do you see here? Cause?

- Necrotizing, nodular lesions in the lung (become cavitating when largest and most advanced) 

- Characteristic of: granulomatosis with polyangiitis 


What is this?

- Geographic necrosis in granulomatosis with polyangiitis 


What do you see here?

- Multinucleated giant cells -> granulomatosis with polyangiitis 


What is this?

- Lung vasculitis 

- Granulomatosis with polyangiitis (affects both arteries and veins) 


What is going on here?

- Kidney with very small, tan nodular lesions in the medulla 

- Granulomatosis with polyangiitis 


What is going on in this interlobar artery in the kidney?

- Severe necrotizing vasculitis (low power trichrome stain) 

- Granulomatosis with polyangiitis 


What are the treatment and prognosis for granulomatosis with polyangiitis?

- Treatment: corticosteroids + either cytotoxic immunosuppressive therapy OR targeted therapy with Rituximab (anti-CD20)

- Prognosis: variable


What is allergic granulomatosis with polyangiitis?

- Aka, Churg Strauss syndrome

- Triad of asthma, eosinophilia, and vasculitis 

- Pathology: granulomatosis with polyangiitis + lots of eosinophils (simplified version)

- Image: necrotizing vasculitis 


What is going on here?

- Allergic granulomatosis with polyangiitis (Churg Strauss) 

- Numerous eosinophils recognizable by their red cytoplasma and bilobed nuclei (high power image of necrotizing vasculitis) 


What is this from? Describe the disease and treatment.

- Buerger Disease (thrombangiitis obliterans)

- Uncommon; young male Middle Eastern or South Asian smokers 

- Inflammatory, thrombosing vaso-occlusive disease of arteries and veins of limbs 

- Typically present with toe pain (+/- fingers), followed by ischemic ulcers, then gangrene -> distal to proximal 

- Pathology

1. Acute - segmental, transmural acute inflam w/o necrosis + thromboses + granulomas + giant cells 

2. Chronic - non-specific organization and recanalization of thrombus + neovascularization + fibrosis 

- Tx: stop smoking and amputate gangrene 


What do you see here? What might have caused this?

- Necrotic muscle around a thrombosed vein 

- Buerger disease (thromboangiitis obliterans) 


What do you see here? Just describe what this is.

- Chronic inflammation around an organized thrombus



What is peripheral arterial disease (PAD)? What are the signs and symptoms?

- Chronic atherosclerotic arterial disease of large and medium arteries, primarily of the legs 

- Common, primarily in the elderly (more comm in M)

- Symptoms: intermittent claudication (limb pain brought on by exercise and relieved by rest) 

1. Calf mm when disease in femoral, popliteal aa

2. Severe disease: pain at rest, ulcers 

- Signs: diminished/lost pulses, bruits (swishing sounds auscultated over lesions w/turbulent flow), pallor (or cyanosis), skin or muscle atrophy, ulceration, necrosis (gangrene)


What is this? How do you dx and treat this disease?

- Debrided leg ulcer from peripheral arterial disease (PAD)

Diagnosis: history and physical exam 

Treatment: exercise, esp. walking (develops collateral circulation) 


Tell me everything about acute arterial occlusion.

- Uncommon 

- Usually due to thromboemboli

1. 80% from heart: 65% mural from MI, 10% left atrial (atrial fibrillation, mitral stenosis), 5% dilated cardiomyopathy

2. 20% unidentifiable/miscellaneous sources 

- Signs and symptoms: FIVE P's -> paralysis, pallor, pain, paresthesia, and pulselessness in legs (70%) or arms (8%)

1. 10% are in the brain (o/sites include intestines, kidneys, and spleen)

- Diagnosis: history & physical examination

- Treatment: anticoagulation (heparin), intra-arterial thrombolytic therapy, catheter-based thrombectomy, surgery (thrombectomy, bypass)

- NOTE: acute arterial occlusion is often a SURGICAL EMERGENCY