Vascular Pathology Flashcards
What is an AVM?
Arteries and veins without intervening capillaries
“Tangle of worms” with pulsatile arteriovenous shunting with high blood flow is indicative of what?
AVM
AVM causes what type of cardiac failure?
High-output
Due to shunting of blood into venous circulation
In what population does AVM occur more frequently?
Males
When is AVM typically diagnosed?
Childhood
What is a surgically created AVM?
Arteriovenous fistula for hemodialysis or chemotherapy
What AVM can cause hematuria?
AVM of bladder
What are symptoms of an AVM of the brain?
Seizure
Intracerebral hemorrhage
What is a focal abnormality of an artery due to underlying defect in the media?
Berry (saccular) Aneurysm
Where is a berry (saccular) aneurysm typically found?
Anterior cerebral artery
Anterior communicating artery
What are risk factors for berry (saccular) aneurysm?
HTN
Smoking
Berry (saccular) aneurysms are associated with which diseases?
AD Polycystic kidney disease
Marfan syndrome
Ehlers Danlos syndrome
Subarachnoid hemorrhage is associated with what?
Berry (saccular) aneurysm
What are symptoms of a subarachnoid hemorrhage?
Neck pain Vomiting Double vision Seizures LOC
Berry (saccular) aneurysm rupture often happens with what?
Straining with stool
Sexual orgasm
What is a dilation of artery due to infectious process that damages the vessel wall?
Mycotic aneurysm
What are the three causes of mycotic aneurysm?
1) Septic emboli (infective endocarditis)
2) Extension of an adjacent infectious process
3) Circulating organisms directly infecting the arterial wall
What is a focal, irregular thickening of medium and large muscular arteries?
Fibromuscular dysplasia
What arteries does fibromuscular dysplasia typically impact?
Renal
Carotid
Splanchnic
Vertebral
Fibromuscular dysplasia is upregulated in women due to what?
Estrogen
Fibromuscular dysplasia shows what on angiography?
String of beads
What artery does fibromuscular dysplasia most commonly impact?
Renal artery
Renal artery stenosis in fibromuscular dysplasia leads to activation of what?
RAAS
Activiation of RAAS in renal artery stenosis results in what?
Renovascular HTN (bruit sometimes heard)
What maintains blood volume and vascular tone?
Renin-angiotensin-aldosterone system
When is renin released?
Low volume
Low peripheral resistance
Decreased glomerular filtration rate
Where is renin released?
By juxtaglomerular cells in the afferent arterioles in the kidneys
Renin cleaves circulating angiotensinogen to form what?
Angiotensin I
Angiotensin I is cleaved to form angiotensin II by what?
ACE
Angiotensin II does what?
Vasoconstrict
Volume expansion caused the myocardial cells to release what?
Atrial natriuretic peptide
What does atrial natriuretic peptide cause?
Sodium excretion
Vasodilation
Decreased BP
HTN is a risk factor for what?
Atherosclerosis
End organ damage
What are the unmodifiable risk factors for primary HTN?
Age (older)
Genetics (blacks, higher risk)
What are the modifiable risk factors for primary HTN?
Stress
Obesity
Physical inactivity
Increased salt consumption
What are the renal causes of secondary hypertension?
Renovascular disease Renal artery stenosis Fibromuscular dysplasia Atherosclerosis Polycystic kidney disease
What are the endocrine causes of secondary hypertension?
Primary aldosteronism
Cushing syndrome
Pheochromocytoma
What are the cardiovascular causes of secondary hypertension?
Coarctation of the aorta
Primary hyperaldosteronism causes HTN with what?
Hypokalemia
What symptoms are associated with the HTN due to primary alderosteronism?
Neuromuscular changes (weakness, muscle cramps, paraesthesias, visual disturbances)
What are the three causes of hyperaldosteronism?
Bilateral nodular hyperplasia of adrenal gland
Adenoma
Hybrid glomerulosa cells responsive to ACTH
What are the four causes of Cushing syndrome?
Tumor in anterior pituitary
Tumor in adrenal
Paraneoplastic Cushing
Iatrogenic Cushing syndrome (oral steroids)
What is a pheochromocytoma?
Tumor of the chromaffin cells of the adrenal medulla
What is secreted by a pheochromocytoma?
Epinephrine
Norepinephrine
Norepinephrine causes what?
Alpha-1 activation -> peripheral vasoconstriction
Beta-1 activation -> increased cardiac output
Epinephrine causes what?
Beta-1 activation -> increased cardiac output
What are the clinical symptoms of pheochromocytoma?
Paroxysm of elevated blood pressure Tachycardia Palpitations Headache Diaphoresis Tremor
How do you diagnose pheochromocytoma?
Elevation of urinary or plasma metanephrines
What syndrome is pheochromocytomas assocaited with?
MEN 2
What do pheochromocytomas look like on gross examination?
Golden brown color
What is MEN 1?
Pituitary adenoma
Parathyroid hyperplasia
Pancreatic tumors
What is MEN 2A?
Parathyroid hyperplasia
Medullary thyroid carcinoma
Pheochromocytoma
What is MEN 2B?
Mucosal neuromas
Marfanoid body habitus
Medullary thyroid carcinoma
Pheochromocytoma
What is the rule of 10s for pheochromocytomas?
10% are malignant
10% are extraadrenal
10% of sporatic are bilateral
10% are not associated with hypertension
What happens with renal artery stenosis?
HTN
Decreased GFR
Chronic kidney disease
Increased creatinine
What are the two causes of renal artery stenosis?
Atherosclerosis
Fibromuscular dysplasia
What is adult coarctation of the aorta?
Congenital narrowing of the aorta opposite the ligamentum arteriosum
What does adult coarctation of the aorta cause?
HTN in upper extremities
Hypotension in the lower extremities
Limb claudication
What is coarctation of the aorta in adults associated with?
Bicuspid aortic valve
Coarctation of the aorta is most common in what population?
Males
When is a bruit heard?
Significant obstruction of a larger vessel
Where is a bruit heard with renal artery stenosis associated with fibromuscular dysplasia?
Epigastric abdominal bruit which radiates to the back or side
Where is a bruit heard with coarctation of the aorta?
Carotid bruit
Pyelonephritis and polycystic kidney disease can be a secondary cause of what?
HTN
How does parenchymal kidney disease cause hypertension?
Activation of the renin-angiotensin system due to renal ischemia
Why does concentric left ventricular cardiac hypertrophy occur?
Left ventricle is attempted to pump blood against increased vascular resistance
Concentric left ventricular cardiac hypertrophy leads to what?
Cardiomegaly (which then leads to heart failure, which then leads to fluid back up in the lungs, which then leads to dyspnea)
What are heart and aorta effects due to HTN?
Cardiac hypertrophy
Chronic heart failure
Ischemic heart disease
Aortic dissection
What are kidney effects due to HTN?
Proteinuria
What are brain and eye effects due to HTN?
Multi-infarct dementia
Cerebrovascular hemorrhage/strone
Increased intracranial pressure/papilledema (headache/vision changes)
Retinopathy (AV nicking)
What do patients with untreated HTN die from?
Ischemic heart disease/CHF
Stroke
Hyaline arteriosclerosis due to what?
Increased smooth muscle matrix synthesis and plasma protein leakages across damaged endothelium
Which drug class is hyaline arteriosclerosis seen in?
Calineurin inhibitors (T-cell immunosuppressive drug)
What is the hyaline material composed of in hyaline arteriosclerosis?
Precipitated plasma proteins
C3
Hyaline arteriosclerosis can lead to what downstream?
Ischemia
Homogenous pink (hyaline) thickening of the vessel wall leads directly to what?
Luminal narrowing
Hyaline arteriosclerosis manifests as what in the kidney?
Hyaline nephrosclerosis
Hyaline nephrosclerosis causes what?
Impairment of renal blood supply
Ischemic glomerulosclerosis
Leads to RAAS activation -> HTN
What is a hypertensive crisis?
Systolic greater than 180-200
Diastolic greater than 120
What is a hypertensive emergency?
Hypertensive crisis with end organ damage
What end organ damage is seen in hypertensive emergencies?
Renal failure Encephalopathy Acute heart failure Retinal hemorrhages and exudates Papilledema
Papilledema is typically found with what?
Increased CSF pressure
What does the kidney show in hypertensive emergencies?
Necrotizing arteriolitis
Hematuria
Increased creatinine
Renal failure
What is malignant hypertension?
Markedly increased hypertension
Hyaline arteriolosclerosis occurs with what type of hypertension?
Chronic
Hyperplastic arteriolosclerosis occurs with what type of hypertension?
Severe
In hyperplastic arteriolosclerosis the smooth muscle forms what?
Concentric lamellations with a thickened reduplicated basement membrane
“Onion skinning” is found in what type of arteriolosclerosis?
Hyperplastic
What accompanies lamellations in malignant hypertension?
Fibrinoid deposits
Vessel wall necrosis (especially in the kidney)
Hyaline arteriolosclerosis causes what kidney appearance?
Cortical scarring
Shrunken kidney with granular surface
Thinned cortex
Hyperplastic arteriolosclerosis causes what kidney appearance?
Numerous petechial hemorrhages
What does arteriosclerosis mean?
Hardening of the arteries
Arterial wall thickening
Loss of elasticity
What are the three types of arteriosclerosis?
1) Arteriolosclerosis
2) Atherosclerosis
3) Monckeberg medial sclerosis
What are the two types of arteriolosclerosis?
Hyaline
Hyperplastic
In what vessels does arteriolosclerosis occur?
Small arteries and arterioles
What are complications of arteriolosclerosis?
Downstream ischemic injury
What happens in atherosclerosis?
Atheromatous plaque formation
What are complications with atherosclerosis?
Stenosis/occlusion Plaque rupture Aneurysm Thrombus Atheroembolism Microemboli
What is Monckeberg medial sclerosis?
Calcification of muscular arteries and internal elastic membrane
What type of arteriosclerosis is an age related degenerative process?
Monckeberg medial sclerosis
What is the number one cause of death in the US?
Myocardial infarction
What are the nonmodifiable risk factors for aterosclerosis?
Genetic abnormalities
Family history
Increasing age
Male gender
What is the genetic inheritance for atherosclerosis?
Multifactoral inheritance (AD= familial hypercholesteremia)
At what age is atherosclerosis most common?
40-60s
Increasing age= increasing risk
What is a protective effect for atherosclerosis?
Premenopausal estrogenized women (only younger women)
What is the most important factors for developing atherosclerosis?
Genetic predisposition
Are risk factors for atherosclerosis synergistic or additive?
Synergistic
What are modifiable risk factors for atherosclerosis?
Hyperlipidemia Hypertension Cigarette smoking Diabetes Metabolic syndrome Inflammation Hyperhomocysteinemia Lipoprotein a Factors affecting homeostasis Lack of exercise Competitive, stressful lifestyle Obesity
Which cholesterol delivers cholesterol to peripheral tissues?
LDL
Which cholesterol mobilizes cholesterol from the periphery?
HDL
How do statins work?
Inhibit HMG-CoA reductase (enzyme key in producing LDL cholesterol)
Decreases LDL, increases HDL
How can HDL be increased?
Exercise
Moderate alcohol intake
What decreased HDL?
Smoking
Obesity
What increases LDL?
Animal products Trans fat (fried, snack food)
What decreases LDL?
Soluble fiber
Statins
How do cigarettes promote atherosclerosis?
ROS and free radicals cause endothelial dysfunction and platelet activation through oxidization of LDL
How does diabetes promote atherosclerosis?
Sugar causes oxidative stress which damages blood vessels and increases inflammation
How does hyperhomocysteine increase aterosclerosis?
Oxidative stress leading to damage of the endothelium
C-reactive protein correlates with what?
Inflammatory activity
Cardiac risk
Pack per day for years doubles risk of what?
Ischemic heart disease
Diabetes doubles your chances of what?
Myocardial infarction
Hyperhomocysteinemia is associated with what?
Increased coronary atherosclerosis
Increased peripheral vascular disease
Increased stroke
What cytokine is associated with c-reactive protein?
IL-6
What makes up metabolic syndrome?
Abdominal obesity Increased triglycerides Low HDL Hypertension Insulin resistance
What is function of endothelium?
Non-reactive barrier that keeps blood and plasma going throughout the body smoothly in laminar flow
What causes endothelial activation?
Turbulent flow Hypertension Cytokines Complement Bacterial products Lipid products Advanced glycation end-products Hypoxia Acidosis Viruses Cigarette smoke
What happens in activated endothelium?
Increased expression of procoagulants
Adhesion molecules and proinflammatory factors
Altered expression of chemokines, cytokines, and growth factors
Activated endothelium is the key to driving the pathogenesis of what?
Atherosclerosis
What are the steps in vascular injury?
1) Recruitment of smooth muscle cells or smooth muscle precursor cells to intima
2) Smooth muscle cell mitosis
3) Elaboration of extracellular matrix
What are the two parts of an atherosclerotic plaque?
Fibrous cap
Necrotic center
What makes up the fibrous cap of an atherosclerotic plaque?
Smooth muscle cells Macrophages Foam cells Lymphocytes Collagen elastin Proteoglycans Neovascularization
What makes up the necrotic center of an atherosclerotic plaque?
Cell debris
Cholesterol crystals
Foam cells
Calcium
Where is fibrous cap located in the atherosclerotic plaque?
Adjacent to the lumen
What is the atherosclerotic plaque surrounded by?
Internal elastic lamina
What happens when vessels become completely occluded?
Neovascularization
What lipid is atheromatous plaques primary consisted of?
LDL (which accumulates in the intima)
When monocytes take up oxidized LDL what cytokine is released to recruit additional monocytes?
IL-1
Where does atherosclerosis typically occur?
Branch points
Posterior abdominal aorta
What are the steps for atherosclerosis?
1) Chronic endothelial injury
2) Endothelial dysfunction
3) Macrophage activation with smooth muscle recruitment
4) Engulfment of lipid with fatty streak deposition
5) Proliferation of smooth muscle with extracellular matrix deposition
Which growth factors are important for smooth muscle cell proliferation and extracellular matrix deposition?
PDGF
Fibroblast growth factor
TGF-alpha
What releases PDGF?
Platelets
Macrophages
Endothelial cells
Smooth muscle cells
What are the most extensively involved vessels with atherosclerosis?
Abdominal aorta
Coronary arteries
Internal carotid arteries
Circle of Willis
What is the earliest gross indication of atherosclerosis?
Superficial flat yellow fatty streaks
What are fatty streaks made of?
Lipid filled macrophages on the intimal surface
What does severe atherosclerosis look like grossly?
Ulcerated plaques with calcification and associated blood clots
What does a fatty streak turn into?
Fibrofatty plaque
What causes a fibrofatty plaque to turn into an advanced/vulnerable plaque?
Cell death/degeneration Inflammation Plaque growth Remodeling of plaque and wall extracellular matrix Organization of thrombus Calcification
What are the three clinical outcomes of atherosclerotic changes?
1) Aneurysm and rupture
2) Occlusion by thrombus
3) Progressive plaque growth
What causes aneurysm and rupture with atherosclerosis?
Mural thrombosis
Embolization
Wall weakening
What causes occlusion by thrombus with atherosclerosis?
Plaque rupture Plaque erosion Plaque hemorrhage Mural thrombosis Embolization
What causes critical stenosis with atherosclerosis?
Progressive plaque growth
What are clinical effects of atherosclerosis on the brain?
Thrombus causes infarction or stroke
Vascular rupture leas to intracerebral hemorrhage
What are clinical effects of atherosclerosis on the kidney?
Renal artery stenosis -> HTN
Ischemic injury with uremia
Renal failure
What is the principle cause of abdominal aortic aneurysms?
Atherosclerosis
Obstruction of visceral organs due to atherosclerosis causes what?
Chronic mesenteric ischemia nd infarction
Peripheral vascular disease causes what?
Claudication
Gangrene
Atherosclerosis can cause what in the heart?
Ischemic heart disease -> stenosis -> myocardial infarction
What is an excessive locational abnormal dilation of a blood vessel or ventricular wall?
Aneurysm
What is a “true” aneurysm?
Intact but thinned muscular wall at the site of dilation
What is a “false” aneurysm?
Defect though the wall of the vessel communicating with an extravascular hematoma that freely communicates with the intravascular space (pulsating hematoma)
What arises when blood enters a defect in the arterial wall and tunnels between layers?
Arterial dissection
Which aneurysm bulges out on one side?
Saccular
Which aneurysm bulges out on all sides of the vessel?
Fusiform
Where does a ventricular aneurysm occur?
Site of previous MI
What is cystic medial degeneration?
Normal elastin of the media is disrupted and replaced with areas of amorphous ground substance
What causes cystic medial degeneration?
Marfan
Ehlers Danlos
Systemic HTN
How does systemic HTN cause cystic medial degeneration?
Narrowing of small arterioles which feed the aorta leading to aortic ischemia, scarring, and inadequate ECM synthesis
What do vessels with cystic medial degeneration look like in Marfan syndrome?
Elastin fragmentation with areas without elastin fibers that are filled with proteoglycans
Marfan syndrome is caused by a mutation in what gene?
FBN1 (fibrillin gene)
What does the FBN1 or fibrillin gene do?
Needed for structural integrity of connective tissue
Is there increased or decreased TGF-beta in Marfan syndrome?
Increased
In Marfan syndrome fibirllin in unable to bind what?
TGF-beta
Increased TGF-beta activity weakens what?
Elastic tissue
What are symptoms of Marfan syndrome?
Tall stature Long fingers Subluxation/dislocation of lenses Pectus excavatum Mitral valve prolapse Aortic aneurysm Aortic dissection
Ehlers danlos is due to a mutation in what?
Collagen
What are symptoms of ehlers danlos?
Hyperelastic, fragile skin Joint hypermobility Lens subluxation Abnormal wound healing Widened scars Bruising Mitral valve prolapse Kyphscoliosis Rupture of colon, cornea, large arteries
What is syphillis caused by?
Spirochete Treponema pallidum
What skin lesion is seen on initial infection with syphillis?
Red chancre lesion in the genital or anal area
Tertiary syphillis presents after a latency period of how long?
5 years
What organ systems does tertiary syphillis impact?
Brain (neurosyphillis) Skin Bones Organs (gumma formation) Heart (obliterative endarteritis)
What is a gumma formation?
Plasma rich inflammatory lesions
What is obliterative endarteritis?
Concentric endothelial and fibroblastic proliferation of small vessels
Where does obliterative endarteritis occur with tertiary syphillis?
Vaso vasorum (which feeds thoracic aorta causing ischemia and aneurysm formation)
What two cardiovascular conditions occur with tertiary syphillis?
Obliterative endarteritis
Aortitis
What appearance does an aortic aneurysm due to tertiary syphillis have?
Tree bark appearance (aorta becomes rough and pitted with concomitant calcification)
What is the most important risk factor for abdominal aortic aneurysms?
Atherosclerosis
What are risk factors for abdominal aortic aneurysms?
Smoking
Male
Age
What is the typical location for abdominal aortic aneurysms?
Below renal arteries, above aortic bifurcation
What do abdominal aortic aneurysms typically contain?
Bland laminated mural thrombus
What vasculature does abdominal aortic aneurysms impact?
Renal
Superior mesenteric arteries
Iliac arteries
How do the major of AAA patients present?
Aymptomatically
In 1/3 of asymptomatic AAA patients there is what?
Pulsatile abdominal mass
In 2/3 of asymptomatic AAA patients it is found during what?
Radiology finding or work up for peripheral vascular disease
What are the non-ruptured symptoms of AAA?
Pain in abdomen, back
What are the ruptured symptoms of AAA?
Severe acute pain
Pulsatile abdominal mass
Hypotension
What is the size of AAA where surgical bypass is considered?
5 cm
5-10% of AAA are what type?
Inflammatory with abundant lymphoplasmacytic inflammation
What is a chronic inflammatory disease thought to represent an autoimmune disease in which numerous lymphocytes and IgG4 secreting plasma cells are associated with prominent fibrosis?
IgG4 related disease
What organs is IgG4 related disease most common?
Pancreas (autoimmune pancreatitis) Biliary tree (sclerosing cholangitis) Major salivary glands Orbit of eye Retroperitoneum
What happens in IgG4 related disease and AAA?
Weakening of the wall with a fibroinflammatory infiltrate
What treats IgG4 disease?
Steroids
What is seen on histology of IgG4 disease with AAA?
Spindle fibroblastic-type cell proliferation admixed with clusters of plasma cells and lymphocytes
What is primary risk factor for thoracic aortic aneurysm?
HTN
What are conditions associated with thoracic aortic aneurysms?
Tertirary syphillis
Connective tissue disease (Marfan syndrome)
Vasculitis (giant cell aortitis, Takayasu)
What are clinical symptoms of thoracic aortic aneurysms?
Breathing difficulties
Dysphagia
Cough (recurrent laryngeal nerve)
When is surgical repair or endovascular placement of graft material considered for thoracic aortic aneurysm?
5.5 cm
What is the clinical triad for aortic dissection?
1) Abrupt onset of thoracic pain with a sharp, tearing or ripping character
2) Variation of pulse (absence of proximal extremity or carotid pulse) and a greater than 20 mim of mercury BP difference between arms
3) Mediastinal widening on CXR as blood expands the vessel
Where is the pain in aortic dissection?
Radiates to the back and move downward as dissection progresses
How does death occur with aortic dissection?
Rupture of dissection through the adventitia into the pericardial, pleural, or peritoneal cavities
Is cystic medial degeneration associated with aortic dissection?
Yes
What are the two caused os aortic dissection?
1) HTN (men, 40-60)
2) Connective tissue disorders (Marfan syndrome, Ehlers Danlos)
A tear in the intima of the aorta causes development of what?
Hematoma
How does a hematoma become a dissecting aneurysm?
Hematoma in the media dissects longitudinally
What is a double barreled aorta?
Intimal tear further down the aorta that reconnects the false lumen back to the aorta
How does a false aneurysm become a chronic dissection?
False channel is endothelized overtime
Do chronic dissections have the potential for future rupture?
Yes
What is type A dissection?
Proximal intimal tear in the ascending aorta
What is the most common type of aortic dissection?
Type A
What is a type B dissection?
Proximal intimal tear in the aortic arch or the descending arota
Which type of aortic dissection is more prone to external rupture into the mediastinum or pericardial cavity requiring surgical intervention?
Type A
How are uncomplicated type B dissections handled?
Medical management
What are the large vessel vasculitis?
Giant cell arteritis
Takayasu arteritis
What are the medium vessel vasculitis?
Polyarteritis nodosa
Kawasaki disease
What are the small vessel vasculitis?
Microscopic polyangiitis Wegener granulomatosis Churg-Strauss syndrome SLE vasculitis Henoch-Schonelin purpura Cryoglobulin vasculitis Goodpasture disease
What is the most common vasculitis in older adults in the US?
Giant cell arteritis
What is a T-cell mediated vasculitis that affects the arteries of the scalp and head?
Giant cell arteritis
What is the most common feature of giant cell arteritis?
Headache
also facial pain, fever, ocular diagnoses, fatigue/flu like symptoms
Ocular symptomatology occurs in half the patients with what?
Giant cell arteritis
Why is it important to catch giant cell arteritis quickly?
Can spread to ophthalmic artery and cause permanent blindness
What is used to diagnose giant cell arteritis?
Temporal artery biopsy
How is giant cell arteritis treated?
High dose corticosteroids
What is seen on the temporal biopsy for someone with giant cell arteritis?
Intimal thickening with granulomatous inflammation and fragmentation of the internal elastic lamina
Which vasculitis is a granulomatous autoimmune vasculitis associated with certain HLA subtypes?
Takayasu arteritis
What populations are primarily affected by Takayasu arteritis?
East Asia
India
Latin America
What age and gender is most commonly associated with Takayasu arteritis?
Female aged 15-40
What are the symptoms of Takayasu arteritis?
Ocular disturbances Weakened pulses in upper extremities Fatigue HTN Fever Decreased weight
What is seen on histology for Takayasu arteritis?
Perivascular mononuclear infiltrate which can evolve to marked destruction with fibrosis and giant cells
What is a systemic vasculitis of small to medium vessels associated with hepatitis B?
Polyarteritis nodosa
What age group is typically affected by polyarteritis nodosa?
Young adults
What is the pathophysiology associated with polyarteritis nodosa?
Immune complex mediated disease with Hep B surface antigen/Hep B surface antibody complexes in vessels
What vessels does polyarteritis nodosa impact the most?
Renal vessels Heart Liver GI tract Peripheral nerves Skin
What is seen histologically with polyarteritis nodosa?
Fibrinoid necrosis with embedded inflammatory cells within the wall
How does polyarteritis nodosa typically present?
Rapidly accelerating HTN (renovascular HTN) Abdominal pain Hematochezia Myalgias Peripheral neuritis of the motor neurons
Polyarteritis nodosa is fatal with renal involvment unless given what therapy?
Immunosuppression
What is an acute multisystem vasculitis of large to medium vessels which presents in early childhood and infancy?
Kawasaki disease
What are the symptoms of Kawasaki disease?
Conjunctivitis Rash (genital) Adenopathy (cervical) Strawberry tongue Hands (palmar erythema and swelling) Burn (fever)
Kawasaki disease has a preference for which artery?
Coronary artery
What causes Kawasaki disease?
Activated T cells (+ monocytes/macrophages) which are provoked by a viral illness
What causes death in Kawasaki disease?
Aneurysmal rupture of coronary arteries
Depress ventricular function can result in which vasculitis?
Kawasaki disease
What is given to treat Kawasaki disease?
Aspirin and IVIG
What is another name for Kawasaki disease?
Mucocutaneous lymph node syndrome
What is a small vessel vasculitis with upper respiratory involvement, asthma, peripheral blood esosinophilia, and pulmonary infiltrates?
Churg-Strauss syndrome
What are found in a biopsy for Churg-Strauss syndrome?
Eosinophils with granulomas
What lab finding is positive for Churg-Strauss syndrome?
MPO-ANCAs
What organs systems are involved in Churg-Strauss syndrome?
Skin (palpable purpura)
GI tract bleeding
Renal disease (focal and segmental glomerulosclerosis)
What causes death in patients with Churg-Strauss?
Cardiomyopathy/myocarditis with infarction
How is Churg-Strauss treated?
Steroids
Cyclophosphamide
What is a necrotizing granulomatous vasculitis which affects small to medium sized vessels of the upper and lower respiratory tract including the sinonasal tract and lung?
Granulomatosis with polyangiitis/Wegner’s granulomatosis
What respiratory tract conditions are seen in granulomatosis with polyangiits?
Pneumonia with infiltrates
Chronic sinusitis
Nasopharyngeal ulceration
What renal conditions is seen with granulmatosis with polyangiitis?
Necrotizing crescentic glomerulnephritis
What population is most commonly affected with granulomatosis with polyangiitis?
Middle aged
What is the pathogenesis of granulomatosis with polyangiitis?
T-cell hypersensitivity reaction mediated by inhaled environmental or microbial material
What serologic test can identify granulomatos with polyangiits?
PR3-ANCA (C-ANCA)
What lung findings are seen with granulomatosis with polyangiitis?
Cavities
Bleeds
Infiltrates
What nasal findings are seen with granulomatosis with polyangiitis?
Stuffiness
Nose bleeds
Saddle nose
What is the treatment for granulomatosis with polyangiitis?
Steroids
Cyclophosphamide
TNF-antagonists
What lesions are seen on histology with granulomatosis with polyangiitis in the lung?
Tan, nodular centrally cavitating lesions
What lesions are seen on histology with granulomatosis with polyangiitis in the kidney?
Necrotizing crescentic glomerulonephritis
Which vasculitis has uniform stage of disease activity in all vessels?
Microscopic polyangiitis
What are the symptoms associated with microscopic polyangiitis?
Hematuria Proteinuria Hemoptysis Cutaneous purpura Muscle weakness Bowel pain Bleeding
Is there deposition of immunoglobin in microscopic polyangiitis?
No
What is found on histology for microscopic polyangiitis?
Leukocytoclastic picture with neutrophils infiltrating small blood vessels
What vessels does microscopic polyangiitis impact?
Arterioles
Capillaries
Venules
Various stages of disease activity are seen within different vessels in what vasculitis?
Polyarteritis nodosa
What is the classic triad for Behcet’s disease?
1) Oral aphthous ulcers
2) Genital ulcers
3) Uveitis
What HLA is Behcet’s disease associated with?
HLA-B51
What is seen in the GI system with Behcet’s disease?
Ulcerations
What inflammatory cell is required for diagnosis of Behcet’s disease?
Neutrophils
How is Behcet’s disease treated?
Steroids
TNF-antagonists
What is another name for thromboangiitis obliterans?
Berger disease
What arteries does thrombangiitis obliterans typically impact?
Tibial artery
Radial artery
What occludes the vessel in thromboangiitis obliterans?
Microabscess (granulomatous)
What population is thromboangiitis obliterans found?
Smokers > 35 years old
What is the pathophysiology of thromboangiitis obliterans?
Hypersensitivty/toxic reaction to cigarette smoke
Anti-endothelial antibodies
What ethnic groups are commonly affected with thromboangiitis obliterans?
Israeli
Indian
Japanese
What is the symptom progression for thromoangiitis obliterans?
Raynaud’s -> intermittent claudication -> sever pain at rest -> ulceration -> gangrene
What is the pain in claudication due to?
Lack of oxygen in tissues
Raynaud is secondary to what diseases?
Systemic lupus
Scleroderma
Thromboangiitis obliterans
What provokes an attack of Raynaud’s?
Cold temperature
Emotion
Stress
Is primary Raynaud’s symmetric or asymmetic?
Symmetric
Does primary or secondary Raynaud’s spontaneously remit?
Primary
The aorta is involved in which vasculitis?
Giant cell arteritis
Takayasu arteritis
Eosinophils are rare in which vasculitis?
Giant cell arteritis
Eosinophils are required in which vasculitis?
Churg-Strauss
Neutrophils are required in which vasculitis?
Behcet disease
Granulomas are required in which vasculitis?
Granulomatosis with polyangiitis
Thrombosis is required in which vasculitis?
Berger disease
PR3-ANCA is positive in which vasculitis?
Granulomatosis with polyangiitis
MPO-ANCA is positive in which vasculitis?
Churg-Strauss
Leukocytoclastic vasculitis
Which vasculitis is associated with polymyalgia rheumatica?
Giant cell arteritis
Which vasculitis is associated with asthma, atopy, and sinusitis?
Churg-Strauss syndrome
Which vasculitisis is associated with Hep B?
Polyangiitis nodosa
Which vasculitis is associated with young smokers?
Berger disease
Which vasculitis is associated with orogenital ulcers?
Behcet’s disease
What is thought of as a cardiac Raynaud’s phenomenon?
Myocardial vessel vasospasm
What are the three main causes of myocardial vessel vasospasm?
1) High levels of vasoactive mediators
2) Elevated thyroid hormones
3) Autoantibodies and T-cells in scleroderma
What is excessive vasoconstriction of myocardial arteries or arterioles causing ischemia or infarct?
Myocardial vessel vasospasm
What are the sources of high levels of vasoactive meditors?
Exogenous (cocaine, caffeine)
Endogenous (epinephrine/norepinephrine in pheochromocytoma)
What is Takotsubo cardiomyopathy?
“broken heart syndrome”
What is the pathophysiology of Takotsubo cardiomyopathy?
Emotional distress causes sudden surge of catecholamines which stimulates cardiac muscle cells and triggers constriction of coronary arteries (leads to ischemic cardiomyopathy or death)
Hyperthyroidism with elevated thyroid hormone increases the sensitivity to what?
Catecholamines (leading to vasospasm)
What population is broken heart syndrome seen in?
Elderly women
What are varicose veins?
Abnormally dilated twisted veins which occur from prolonged, increased intraluminal pressure leading to incompetence of the venous valves and dilation
Which veins do varicose veins typically occur with?
Superficial veins (with stasis, edema, and thrombosis)
What is stasis dermatitis?
Ischemia of overlying skin with hemolysis of extravasated RBCs and ulcerations
What does the skin look like with varicose veins?
Yellow and shiny (due to extravasated RBCs)
Is embolism common with varicose veins?
No
Is pruritis associated with varicose veins?
Yes
What does portal hypertension lead to?
Esophageal varices Splenomegaly Hemorrhoids Distended superficial epigastric veins Caput medusae
What causes superior vena cava syndrome?
Compression or invasion of the superior vena cava which causes obstruction of blood flow
What is the most common cause of superior vena cava syndrome?
Intrathoracic malignancy
What are the two most common malignancies that cause superior vena cava syndrome?
Bronchogenic lung carcinoma
Lymphoma
What are other causes of superior vena cava syndrome?
Aneurysm
AV fistula
Mediastinal fibrosis
What are the symptoms of superior vena cava syndrome?
Dilation of veins of head, neck, chest, and arms
Cyanosis
Facial swelling
Neurologic manifestations
Respiratory distress (pulmonary vessels compressed)
Confusion
Headaches
Exacerbated as the patient bends forward/lies down
What causes inferior vena cava syndrome?
Hepatocellular carcinoma
Renal cell carcinoma
Thrombosis (DVT)
Tumoral vein invasion
What are the symptoms of inferior vena cava syndrome?
Lower extremity edema
Distension of superficial lower abdominal veins
What is a venous thrombosis with an associated inflammatory response due to clot formation?
Thrombophlebitis
What is thrombophlebitis usually caused by?
DVT of the leg
What are the symptoms of thrombophlebitis?
Edema
Cyanosis
Erythema
Pain
What is the most serious potential consequence with thrombophlebitis?
Pulmonary embolism
What is the most important risk factor for thrombophlebitis?
Prolonged inactivity/immobilization
What are risk factors for thrombophlebitis?
Prolonged inactivity/immobilization Hypercoagulability states (clotting factor mutations, tumor, estrogenic states, factor V leiden) Tumor: thrombotic paraneoplastic syndrome; migratory thrombophlebitis (trousseau sign)
Mucin produdcing adenocarcinomas are thought to be more what?
Thrombogenic
What is a paradoxical embolus?
Embolus crosses from venous to arterial circulation (patent ductus arteriosus, AV malformation, ASD)
What is the most common cause of lymphangitis?
Group A beta-hemolytic streptococcus
How does lymphangitis due to beta-hemolytic streptococcus present?
Erythematous, warm streaking
Cellulitis
Abscess formation with fever
Inflamed lymphatics present as?
Red, painful subcutaneous streaks
Lymphadenitis presents as?
Painful enlargement of draining lymph nodes
What is lymphedema?
Swelling caused by fluid buildup due to blockage of lymphatics
When does lymphedema occur in the axilla?
After axillary dissection
What are the primary causes of lymphedema?
Congenital defect
Familial Milroy disease (lymphatic agenesis/hypoplasia)
What are secondary/obstructive causes of lymphedema?
Malignant tumor
Surgical procedures (radical mastectomy with axillary node dissection)
Post-irradiation fibrosis
What is peau d’orange?
Draining lymphatics of skin overlying breast cancer filled with tumor cells
What is vascular ectasia?
Local dilation of a blood vessel
What is nevus simplex?
Simple birth mark caused by a vascular ectasia in the upper dermis which is extremely common
Does nevus simplex regress with time?
Yes
What is another name for port-wine stains?
Nevus flammeus
What are port wine stains?
Progressive actasisias that persist into adulthood
What is Sturge-Weber syndrome?
Trigeminal nerve facila port wine stain Mental retardation, seizures, hemiplegia Leptomeningial capillary-venous malformation Skull radio-opacitis Eye abnormalities: glaucoma
A large facial telangiectasia in a child with mental deficiency would be a prototypical clinical presentation of what?
Sturge-Weber syndrome
What causes Sturge-Weber syndrome?
Somatic mutations in fetal ectodermal tissue causes inappropriate maturation of blood vessel formation (not heritable)
Where does a nevus simplex typically occur?
Forehead
Eyelid
Nose
Upper lip
What is a non-neoplastic permanent dilation of small vessels and capillaries?
Telangectasia
When is a spider telangiectasia seen?
Increased circulating estrogen levels (mostly seen on face, neck, and upper chest)
Which hormone has dilating effects on small vessels causes telangiectasias?
Estrogen
What are two conditions with hyperestrogenism?
Pregnancy
Liver Cirrhosis
What causes impaired metabolism and inactivation of estrogen leading to increased estrogen?
Liver cirrhosis
What is another name for hereditary hemorrhagic telangiectasia?
Osler-Weber-Rendu disease
What is the inheritance pattern for hereditary hemorrhagic telangiectasia?
Autosomal dominant
What is mutated in hereditary hemorrhagic telangiectasia?
TGF-beta signaling
What happens in hereditary hemorrhagic telangiectasia?
Numerous telangectasias
AV malformations
What are the symptoms associated with hereditary hemorrhagic telangiectasia?
Nosebleeds
GI
Hematuria
What is a benign vascular tumor characterized by an increased proliferation of blood vessels filled with blood?
Hemangiomas
In which populations are hemangiomas common in?
Infancy
Childhood
Where are hemangiomas typically found?
Head
Neck
Is malignant transformation of hemangiomas common?
No
Von Hippel-Lindau has what type of hemangiomas?
Cavernous hemangiomas (vascular lesions in cerebellum, brain stem, retina, pancreas, liver)
Where is pyogenic granulomas most common?
Lips
Mouth Fingers
What is another name for pyogenic granulomas?
Lobular capillary hemangioma
What are some associations with Von Hippel-Lindau?
Angiomatosis
Hemangioblastomas
Pheochromocytoma
Renal cell carcinoma
Pancreatic cysts (pancreatic serous cystadenoma)
Endolymphatic sac tumor
Bilateral papillary cystadenomas of the epididymis or broad ligament of the uterus
What is the most common hemangioma?
Capillary hemangioma
What is seen with capillary hemangiomas?
Red spot
Thin-walled capillaries, tightly packed together
What is a strawberry/congenital/infantile/juvenile hemangioma?
Capillary hemangioma that is present at birth and regresses
What is characteristic of cavernous hemangiomas?
Irregular, dilated vascular channels making a lesions with an indistinct border
Involves deep tissue, more likely to bleed
Pyogenic granuloma is what type of hemangiomas?
Capillary hemangioma
Where are pyogenic granulomas most common?
Oral mucosa
Finger
What is granuloma gravidarum?
Pyogenic granuloma seen in the gingiva of pregnant women
How does congenital juvenile hemangioma/strawberry hemangioma present grossly?
Red bumpy raised plaque
How does congenital juvenile hemangioma/strawberry hemangioma present histologically?
Demarcated lobular collections fo blood vessels
What is seen histologically with cavernous hemaniomas?
Enlarged vessel spaces filled with blood
What is seen histologically with pyogenic granulomas?
Lobulated capillary proliferation of small vessels
What are glomus bodies?
Dermal structures which act as natural arteriovenous shunts
What is the function of glomus bodies?
Take blood away from the skin surface when the skin is exposed to a cold temperature preventing heat loss
What type of cells are glomus cells?
Modified round smooth muscle cells
Glomus tumor is what type of tumor?
Mesenchymal
What does the glomus tumor look like grossly?
Bluish with predilection for the subungal location under the fingernail
What are the symptoms with glomus tumors?
Pain elicited by changes in temperature or tactile stimulation
Are glomus tumors benign?
Yes
What is a lymphangioma?
Benign dermal neoplasm measuring up to 2cm comprised of endothelial lined spaces
What is the key feature of lymphaniomas?
Dilated spaces without RBCs
What is the second main types of lymphangioma?
Cystic hygroma (cavernous lymphangioma)
What conditions are cystic hygromas associated with?
Turner syndrome
Down’s
Klinefelter syndrome
What is the tratment for cystic hygroma?
Surgical excision
Where are lymphangiomas found?
Head
Neck
Axilla
Where are carvernous lymphangiomas found?
Neck
Axilla
Are cavernous lymphangiomas large or small?
Large (>15 cm)
What is a reactive vascular proliferation that is generated in response to Bartonella bacilli?
Bacillary angiomatosis
Bartonella hensale causes what?
Cat scratch disease (necrotizing granulomatous lymphadentitis
Bartonella quintana causes what?
Human body louse which served as a vector for transmitting trench fever in WWI
Bacillary angiomatosis is seen in what populations?
Immunosuppressed (those with HIV, transplant patients)
What is seen clinically with bacillary angiomatosis?
Red, smooth papules and nodules
What is seen histologically with bacillary angiomatosis?
Lobular proliferation of capillaries and ectatic vessels lined by endothelial cells typically with background inflammatory cells such as neutrophils, lymphcytes, and histocytes
What stain is used for bartonella microorganisms?
Warthin-Starry stain
How is bartonella angiomatosis treated?
Antibiotics
What is a vascular neoplasm that requires infection with HHV-8, a double stranded herpes virus?
Kaposi sarcoma
How is Kaposi sarcoma classified?
Intermediate grade
Borderline tumor
What are the symptoms of Kaposi sarcoma?
Red-purple nodules/plaques Lower limbs Genitals Face Back Lymph nodes GI
What are the four types of Kaposi sarcoma?
1) Classic (sporadic)
2) Endemic (African)
3) Iatrogenic (immunosuppresssion related)
4) AIDS associated
What population does classic/sporadic Kaposi sarcoma affect?
Older men of Mediterranean, Eastern European, and Middle Eastern decent
The African endemic variant of Kaposi sarcoma impacts who?
Lymph nodes and viscera of children (HIGH MORTALITY)
Iatrogenic Kaposi sarcoma is assocaited with which drugs?
Calcineurin
What is the most common types of Kaposi sarcoma in the US?
AIDS associated
What are the three stages of Kaposi sarcoma on the skin?
1) Patch stage: red/purple macules
2) Plaques: red, thickened
3) Tumor: nodule formation
What is seen on the histology of the patch stage of Kaposi sarcoma?
Dilated channels containing blood with small hyperchromatic nuclei
What is seen on the histology of the plaque stage of Kaposi sarcoma?
Infiltrative proliferation of spindled endothelial cells and irregular vascular channels
What is seen on the histology of the tumor stage of Kaposi sarcoma?
Nodule mass of spindled cells
What is a malignant tumor of vascular origin?
Angiosarcoma
What are the risk factors for liver angiosarcoma?
Arsenic
Thorotrast
Polyvinyl chorlide (PVC)
What is arsenic used for?
Agricultureal pesticides
Treatment of wood as a preservative pesticide
Well water
What is thorotrast used for?
Radioactive compound that was utilized as a radiocontrast agent for imaging
PVC is what?
Synthetic plastic polymer
When can lymphadema predispose someone to lymphangiosarcoma?
Lymphedema after axillary dissection such as in a radical mastectomy procedure for breast cancer
Radiation therapy can induce mutations which cause what years after initial therapy?
Angiosarcoma
What does angiosarcoma look like histologically?
Well to poorly defined vascular spaces often containing RBCs lined by endothelial cells with cytologic atypia
What stains do angiosarcomas show?
CD31
CD34
When is percutaneous coronary intervention used?
Significant coronary artery disease including patients who have had acute coronary syndrome including ST elevation MI, non-ST elevation MI, and unstable angina
What are the two types of coronary intervention for significant stenosis by atherosclerotic plaque?
Balloon angioplasty
Endovascular stenting
What is given immediately after coronary metallic stents?
Antithromboti drugs
1/3 of patients with traditional metal stents what occurs?
Restenosis
What drives the in-stent restenosis?
Endothelial injury of the stent on the vessel which drives smooth muscle proliferation and matrix synthesis (drug eluting stent in utilized to reduce local neointimal hyperplasia and proliferative in-stent restenosis
What is the anti-restenotic drug used?
Siroliumus
What does a balloon angioplasty do?
Compresses and rupture occluding plaque
Aburpt reclosure can result from thrombosis and spasm
When are vascular grafts utlized?
Replace or bypass a vascular segment involved by significant atherosclerotic disease
When are large synthetic grafts used?
When replacing large vessels like abdominal aortic aneurysm repair
What are two examples of vascular grafts?
Coronary artery bypass grafts
Abdominal aortic aneurysm stent grafting
What occurs in coronary artery bypass grafting?
Native arteries and/or veins are harvested and used to bypass the diseased atherosclerotic vessel
Saphenous veins are easier to harvest and less technically demanding than internal mammary arteries by their failure is?
Higher
What occurs in endovascular abdominal aortic aneurysm repaire?
Endovascular graft device is inserted usually using a femoral artery approach
What is a CABG?
Coronary artery graft
Which artery is used in a CABG?
Internal mammary artery
