Lecture 1: Vascular Pathology (Hillard) Flashcards
At what level of the vasculature is blood pressure controlled?
Arterioles
- primary site of physiologic changes to total peripheral resistance
What is an Arteriovenous Malformation and what 3 things is it caused by (R/P/N)?
What do large AVMs lead to?
- tangle of worm-like arteries connecting to veins WITHOUT intervening capillaries (shunt); most congenital (M > F)
cause: rupture of aneurysm, penetrating injuries, or inflammatory necrosis (connects A to V)
- also SURGICAL –> hemodialysis/chemotherapy
- large AVMs lead to HIGH-OUTPUT CARDIAC FAILURE
What is Berry Aneurysm and where does it most commonly occur?
What are two major risk factors of development?
- abnormal focal dilation of artery due to media defect, usually in CIRCLE OF WILLIS (Anterior Cerebral A. branch point)
RF: hypertension and smoking
What 3 conditions can Berry Aneurysm be associated with (PKD/M/ED) and what does it cause clinically?
What does it feel like?
- AD polycystic kidney disease, Marfans, Ehlers Danlos
- most frequent cause of subarachnoid hemorrhage (“Worst headache of my life doctor”); repeat bleeding common (25-50% die w/rupture)
- neck pain, vomiting, double vision, loss of consciousness, seizures
What is a Mycotic Aneurysm and what is it commonly caused by?
- artery dilation due to vessel wall damage by infection
cause: septic emboli from INFECTIVE ENDOCARDITIS, direct wall infection (circulating)
usually fairly rare
What is Fibromuscular Dysplasia?
What does it look like on angiography and what is a major complication it can cause?
What does it sound like?
- focal, irregular medium/large artery thickening due to medial/intimal hyperplasia (“String of Beads” on angiography)
- first degree relatives have inc. incidence (FEMALES) but not associated w/estrogen or oral contraceptives
- affects RENAL ARTERIES –> Renal Artery Stenosis (activates RAAS; epigastric abdominal bruit)
What are 4 types of Vascular Abnormalities? (B/A/M/F)
- Arteriovenous Fistula
- Berry Aneurysm
- Mycotic Aneurysm
- Fibromuscular Dysplasia
What are 5 humoral constrictors of blood vessels (A/C/T/L/E) and what are 3 humoral dilators of blood vessels (P/K/N) that help determine Peripheral Resistance?
What is a neural constrictor and dilator of blood vessels that helps determine peripheral resistance?
C: angiotensin II, catecholamines, thromboxanes, leukotrienes, endothelin
D: prostaglandins, kinins, nitric oxide (NO)
Neural: Constrictor (alpha-adrenergic) and Dilator (beta-adrenergic)
What are 3 Blood Volume components and 2 Cardiac Factors that determine Cardiac Output?
BV: sodium, mineralcorticoids, ANP
CF: heart rate and contractility
What is the Renin-Angiotensin-Aldosterone System and what does it do?
What is the function of Atrial Natriuretic Peptide?
- helps maintain blood pressure homeostasis
- when BP is low, kidney releases RENIN (juxtoglomerular) that cleaves Angiotensinogen made by the liver, creating ANGIOTENSIN I
- Angiotensin I gets converted to ANGIOTENSIN II by converting enzymes (ACE), allowing it to cause vasoconstriction of vessels, as well as causing adrenals to release more ALDOSTERONE (inc. Na/water reabsorption by kidneys), in order to inc. the BLOOD PRESSURE
- ANP is released by the heart when there is too much volume; ANP vasodilates vessels and causes the kidneys to excrete sodium and water (DECREASES BLOOD PRESSURE)
What is the difference between Primary Hypertension and Secondary Hypertension?
What are 2 unmodifiable and 4 modifiable factors of Primary Hypertension?
- ELEVATED BLOOD PRESSURE (“Silent Killer”) –> leads to End Organ Failure
Primary: 90-95% (idiopathic or essential HTN)
Unmod: inc. age, genetics (African American)
Modifiable: stress, obesity, inactivity, inc. salt
Secondary: 5-10% (causes by other disease process)
- kidney, endocrine, cardiovascular
What are 6 common causes of Secondary Hypertension? (PH/CS/P/RAS/CA/PKD)
- Primary Hyperaldosteronism
- Cushing Syndrome
- Pheochromocytoma
- Renal Artery Stenosis
- Coarctation of Aorta
- Polycystic Kidney Disease
How does Primary Hyperaldosteronism cause Secondary Hypertension?
What is the common feature of Primary Hyperaldosteronism?
- idiopathic hyperaldosteronism (hyperplasia) or adenoma secrete inc. aldosterone, causing increased sodium reabsorption and increased potassium secretion
- Hypertension with HYPOKALEMIA
What are 4 common causes of Cushing’s Syndrome and how does this patient present?
What is Cushing’s Syndrome associated with?
- inc. cortisol production via pituitary tumor (inc. ACTH), adrenal tumor/hyperplasia, paraneoplastic tumor, or steroids
pt: round face, inc. facial hair in women, stretch marks, weight gain in neck/back/belly - cause of Secondary Hypertension
How does Pheochromocytoma cause Secondary Hypertension?
How does a patient present and what test can be done to help confirm the diagnosis?
- tumor of chromaffin cells in the adrenal medulla releases inc. epinephrine/norepinephrine causing inc. cardiac output and constricted blood vessels
- tumor is golden brown and associated with MEN2
C: inc. BP, pounding headache/tremors/sweating
- look for elevated metanephrines in URINE and PLASMA
How does Renal Artery Stenosis cause Secondary Hypertension?
What are two common causes of stenosis?
What noise does this condition make?
- caused by atherosclerosis or fibromuscular dysplasia
- hypertension due to activation of RAAS system (see dec. GFR, chronic kidney disease, inc. creatinine w/ischemia)
abdominal bruit (epigastric) that can radiate to the back
How does Secondary Hypertension due to Coarctation of the Aorta present?
What is a common finding of pts. with this condition?
- hypertension caused by narrowing or constriction of the aorta (pts. usually have BICUSPID AORTIC VALVE)
- will present with HYPERTENSION in upper extremities and HYPOTENSION in lower extremities
What do untreated hypertensive patients usually die from?
What is a common eye finding of patients with hypertension?
- 1/2 die from ischemic heart disease or congestive heart failure, while another 1/3 die from stroke
- pt. with hypertension can have retinopathy with arteriovenous nicking and flame-shaped hemorrhages
What is the difference between Hyaline Arteriosclerosis and Hyperplastic Arteriosclerosis?
Hyaline: due to CHRONIC hypertension
- inc. SM synthesis and C3 protein across endothel.
- pink thickening of walls –> downstream ischemia
Hyperplastic: due to SEVERE hypertension
- SM forms concentric lamellations (“onion skin”)
- basement membrane thickens/reduplicates
What are Hypertensive Crisis and Hypertensive Emergency?
Crisis: rapid inc. in BP > 180-200/120 (ACUTE)
Emergency: hypertensive crisis with END ORGAN DAMAGE
- renal failure, encephalopathy, papilledema
- retinal hemorrhage, acute heart failure
What is Arteriosclerosis and what are its 3 types?
- hardening of the arteries (inc. thickness, dec. elasticity)
- Arteriolosclerosis: hyaline/hyperplastic
- downstream ischemia (small A and arterioles)
- Atherosclerosis: hardening with plaque formation
- stenosis/occlusion and aneurysm
- Monckeberg Medial Sclerosis
- age related degenerative process (no clinical)
- muscular artery calcifications
What is the number 1 cause of mortality in the United States?
Myocardial Infarction (almost 1/4 of all deaths in the United States) –> due to atherosclerosis
Atherosclerotic Risk
What conditions increase and decrease the amounts of LDL and HDL in a patient?
LDL
- inc: animal products, trans fats (fried, snacks) - BAD
- dec: soluble fiber, statins
HDL
- inc: exercise and moderate alcohol
- dec: obesity and smoking
What are the 5 conditions needed to have Metabolic Syndrome (O/T/H/BP/IR)
What does Metabolic Syndrome put patients at inc. risk of developing?
- abdominal obesity, inc. triglycerides, dec. HDL, high BP, insulin resistance
- need at least 3 of the 5
inc. risk of atherosclerosis
How are cigarette smoking, Diabetes Mellitus, hyperhomocysteinemia, and C-reactive protein related to Atherosclerotic Risk?
CS: doubles risk of ischemic heart disease
DM: doubles chance of myocardial infarction
HHC: inc. levels correlate w/inc. coronary atherosclerosis, peripheral vascular disease, stroke
CRP: measure of inflammation, inc. by IL-6
- inc. correlates with inc. cardiovascular risk
What does an atherosclerotic plaque look like on imaging?
- narrowed lumen with a fibrous cap over a cholesterol core (plaque)
- plaque forms on the internal elastic lamina (will be on the outside of the plaque)
- calcifications and neovascularization can be noted as the vessel tries to get alternate blood flow
How do Atherosclerotic Plaques develop?
- LDL enters the intima due to endothelial injury (chronic damage) and is taken up by the macrophages that are trying to help repair the vessel, becoming foam cells
- foam cells cannot get rid of the lipids; they release inc. cytokines to bring more macrophages as a fatty core of necrosis forms
- smooth muscles proliferate around these areas to help try and repair the damage to the vessel; recruited by growth signals sent from the macrophages
Atherosclerotic Plaque Development
What are 3 common growth factors that cause smooth muscle proliferation and collagen deposition?
- PDGF (released by platelets, MO, endothelial cells, SM)
- Fibroblast growth factor
- TGF-alpha
What are the 5 most commonly affected arteries do to atherosclerotic plaques?
LOWER ABDOMINAL AORTA, coronary arteries, popliteal arteries, internal carotid arteries, Circle of Willis
What are 3 clinical outcomes of atherosclerotic plaque formation?
- aneurysm and rupture
- acute plaque rupture = most dangerous problem
- occlusion by thrombus
- critical stenosis
- when 70% dec. in cross-sectional area
all can cause end-organ damage
What is a “True” aneurysm, “False” aneurysm, and arterial dissection?
True: intact (thinned) muscular wall at site of dilation
False: defect through wall of vessel communicating with extravascular hematoma (“pulsating”)
Dissection: blood enters defect in arterial wall and tunnels between its layers
these can RUPTURE, leading to catastrophic problems
What are Marfan Syndrome and Ehlers Danlos Syndrome?
What are pts. with these diseases at inc. risk of developing?
MS: FBN1 fibrillin gene mutation (inc. TGF-b –> elastic tissue weakening)
- tall, long fingers, subluxation, mitral valve prolapse
- inc. risk of aortic aneurysm and dissection
EDS: mutation in collagen (abnormal wound healing)
- hyperelastic, fragile skin; subluxation, mitral prolapse
- inc. risk of aortic dissection (colon/cornea rupture)
What is Tertiary Syphillis and what does it put patients at higher risk of developing?
- STI caused by spirochete T. pallidum presenting >5 yrs after primary infection (chancre lesion)
- causes neurosyphillis, gummas (inflammatory lesions), and CV problems; classic “Treebark” appearance of aorta (rough, pitted aorta w/calcifications)
- inc. risk of obliterative endarteritis of vasa vasorum causing thoracic aneurysm; aortic valve regurgitation can also occur
What is primary risk factor for the development of an Abdominal Aortic Aneurysm and where does it commonly develop?
- ATHEROSCLEROSIS is the major risk factor for Abdominal Aortic Aneurysm (occurs more in smokers and older men > 50 yo)
- commonly develops BELOW renal arteries but ABOVE aortic bifurcation (contains bland laminated mural thrombus)
What is the difference between an Asymptomatic and Symptomatic Abdominal Aortic Aneurysm?
Asymptomatic: majority of cases
- pulsatile abdominal mass with radiology findings
Symptomatic: nonruptured = pain in abdomen and back (MISDIAGNOSIS) or RUPTURE = severe acute pain, pulsatile mass, HYPOTENSION
surgical bypass considered when diameter > 5 cm
What is the Inflammatory-type Abdominal Aortic Aneurysm?
- fibroinflammatory infiltrate due to IgG4 antibodies and circulating plasma cells
- see with pancreatitis and Primary Sclerosing Cholangitis
responds well to steroid therapy
What is the most important risk factor for Thoracic Aortic Aneurysms and what do they cause clinically?
- HYPERTENSION is the most important risk factor (also syphilic aortitis, connective tissue disease, and large vessel vasculitis)
clinical: breathing difficulties, dysphagia, and cough (due to compression and encroachment of structures)
What are the two most common causes of Aortic Dissection and what is the classic triad they present with?
causes: Hypertension (men 40-60) and connective tissue diseases
- intimal tearing w/blood filled channels
Triad: thoracic pain, pulse abnormalities, mediastinal widening on X-RAY (pain radiates to back and down as dissection progresses)
What is the most common dissection of the aorta?
DeBakey 1 - proximal to left common carotid artery
- most common; more prone to rupture
- Debakey 2 - only ascending thoracic aorta
- both are TYPE A dissections
Debakey 3 - Type B; only descending aorta
- can handle with medical management
What is Giant Cell (Temporal) Arteritis?
What antibodies are associated with it?
What is a serious complication of this vasculitis?
- Most Common vasculitis of older adults (F > 50 yo)
- large to small vessels (temporal/vertebral/ophthalmic)
- headache, facial pain, fever
- T-cell mediated autoimmune response (intimal thickening w/granuloma) with anti-endothelial and anti-SM Abs
- can cause VISION LOSS –> diagnosis early to prevent permanent issues (get TEMPORAL Artery BIOPSY)
What is Takayasu Arteritis?
What does it cause clinically?
- granulomatous autoimmune vasculitis of Large and Medium arteries (thickening of aorta and major branch vessels - pulmonary, coronary, renal)
- mononuclear infiltrate with giant cells
- see in F < 50 yo with WEAKENING of upper extremity PULSES and OCULAR DISTURBANCES (+/- fatigue, HTN, fever, dec. weight)
What is Polyarteritis Nodosa (PAN)?
What is it commonly associated with and how does it classically present?
Where is it most commonly found and where is it never found?
- systemic vasculitis of small to medium vessels (young adults due to immune-mediated complex)
- see fibrinoid necrosis
- necrotizing, segmental at BRANCH POINTS
- associated with HEPATITIS B INFECTION
- involves RENAL VESSELS > heart > liver > GI and presents with RAPIDLY ACCELERATING HTN (can be FATAL); peripheral neuritis/myalgias, bloody stools
SPARES PULMONARY VESSELS
What is Kawasaki Disease?
How do pts present? (F/ST/EPS/GR)
- arteritis of Large to Medium vessels (CORONARY ARTERY) in infancy/early childhood (MI in young kid)
- caused by infectious trigger –> activated T Cells and macrophages
- presents with febrile illness, “strawberry tongue”, conjunctivitis, and erythema of palms/soles
- also genital rash
What is Churg-Strauss Syndrome?
What ANCA is it associated with?
- small vessel necrotizing vasculitis w/ASTHMA, HYPEREOSINOPHILIA, LUNG INFILTRATES
- palpable purpura, GI tract bleeds, renal disease (many organ systems can be involved)
- heart is involved in 60% of pts. and can cause cardiomyopathy/myocarditis (1/2 of deaths)
- MPO-ANCA (less than 1/2 have ANCA)
What is Granulomatous w/Polyangiitis (Wegner’s Granulomatosis)?
What ANCA is associated with it?
- small to medium vessel necrotizing granulomatous vasculitis of RESPIRATORY TRACT (+/- necrotizing renal pathology)
- T Cell mediated hypersensitivity in 40 yo MALES
- PR3-ANCA (c-ANCA)
What is Microscopic Polyangiitis?
What ANCA is it associated with?
- necrotizing vasculitis of small vessels (capillaries and venules too)
- uniform stage of disease that affects ANY organ system and have NO significant deposition of immunoglobulin
- MPO-ANCA
What is Behcet’s Disease and what is its triad?
What genetic marker is it associated with?
What finding is required for diagnosis?
- small to medium vessel vasculitis with triad: oral aphthous ulcers, genital ulcers, uveitis (can present with arthritis too)
- associated with HLA-B51
- vasculitis is NEUTROPHILIC (neutrophils REQUIRED for diagnosis)
What is Buerger Disease (Thromboangiitis Obliterans)?
Who is this commonly seen in?
- segmental vasculitis of small and medium vessels of TIBIAL and RADIAL arteries (hands and feet)
- acute/chronic inflammation w/luminal necrosis and granulomatous inflammation in HEAVY SMOKERS < 35 yo (toxic rxn to cigarette process)
- thrombosis –> vascular insufficiency –> ulceration and gangrene
starts as Raynauds phenomenon –> intermittent claudication
What is the difference between Primary and Secondary Raynauds phenomenon?
Primary: symmetric involvement in young women; episodic w/spontaneous remission
Secondary: asymmetric involvement due to SLE, scleroderma, or Buerger Disease (worsens with time)
proximal vasodilation, central vasoconstriction, distal cyanosis
What 3 things (VM/TH/S) cause Myocardial Vessel Vasospasm and what is Takotsubo Cardiomyopathy?
- excessive vasoconstriction due to high lvls of vasomediators (cocaine, caffeine, pheochromocytoma), elevated thyroid hormones, autoantibodies/T Cells (SCLERODERMA)
- TC = “Broken Heart Syndrome” due to emotional stress –> surge of catecholamines (enlarged left ventricle)
What are Varicose Veins?
- abnormally dilated and twisted veins leading to stasis, congestion, edema, ischemia of overlying skin (STASIS DERMATITIS)
- poor wound healing and superimposed infection
What is Portal Hypertension and what 4 findings does it lead to development of?
- venous hypertension due to cirrhosis
- causes esophageal varices, splenomegaly, hemorrhoids (rectum), and caput medusae (distended superficial epigastric veins)
Superior Vena Cava Syndrome vs Inferior Vena Cava Syndrome
S: due to compression/invasion of neoplasms (lung carcinoma or lymphoma)
- marked dilation of veins of head/neck
- respiratory distress, facial swelling (bending over)
I: due to hepatocellular carcinoma, renal cell carcinoma, thrombosis (DVT)
- marked LE edema
- distension of superficial lower abdominal veins
What is Thrombophlebitis?
What is the most serious potential consequence?
- venous thrombosis and inflammation usually in deep veins of LEGS
- due to inactivity, hypercoagulable states, tumor
- presents w/edema, cyanosis, erythema, pain
PULMONARY EMBOLISM is most serious potential consequence
Lymphangitis vs Lymphedema
What is Peau d’ orange?
Lymphangitis: inflammation of lymphatic channels
- due to group A beta-hemolytic strep
- red, painful, SubQ streaks
- lymphadenitis = painful enlarged LNs (draining)
Lymphedema: congenital defect (primary) and blockage of normal lymphatics (secondary)
- malignant tumor, surgical procedure
Peau d’ orange - draining lymphatics of skin overlying skin of breast cancer filled with tumor cells
What is the difference between Nevus Simplex, Port-Wine Stain, and Sturge-Weber Syndrome?
NS: simple birth mark, most common vascular ectasia
- forehead, eyelid, nose –> most regress
PWS: progressive ectasia of vascular plexus
- rare; persists into adulthood
SWS: trigeminal nerve facial port-wine nevi
- mental retardation, seizures, hemiplegia, glaucoma
- leptomeningeal capillary-venous malformation
- skull radio-opacities
Vascular Telangiectasia vs Hereditary Hemorrhagic Telangiectasia
TV: permanent dilation of small vessels/capillaries
- Spider Telangiectasia: radial red lines around center
- face/neck/chest (inc. circulating estrogen)
HHT = Osler-Weber-Rendu Disease
- auto dominant mutation in TGF-b signal pathway
- telangiectasia of organs and mucous membranes
- nosebleeds, GI, hematuria (depends on location)
Hemangioma
What is the difference between Capillary, Congenital, Cavernous, and Pyogenic Hemangiomas?
- common benign vascular tumor (inc. blood vessels filled with blood);
Capillary: red spot, most common, mucosa/viscera
Congenital: at birth, usually regresses; “Strawberry”
Cavernous: indistinct border, more likely to bleed
- usually deeper; associated w/Von Hippel Lindau
Pyogenic: rapidly growing, often in oral mucosa
- type of cavernous hemangioma
- seen in gingiva of pregnant women
What is a Glomus Tumor?
Where are they most commonly located?
- mesenchymal tumor composed of modified SM arising from glomus body (responsible for thermoregulation)
- usually located SUBUNGALLY (bluish tumor); is painful especially with change in temperature or tactile stimulation
- well-circumscribed, bland tumor that is rarely malignant
What is Lymphangioma?
What is the difference between Simple (Capillary) and Cavernous (Cystic) lymphangiomas?
When is Cavernous lymphangioma typically seen?
- benign, lymphatic neoplasm (no RBCs in lumen)
S: around head/neck, axillary predilection
C: neck/axilla of kids; LARGE, massively dilated lymphatic space (fail to communicate with veins)
- seen in Turner’s Syndrome (F 45 XO)
- also Downs/Klinefelters –> hard to resect
What is Bacillary Angiomatosis?
What is used for visualization?
- reactive vascular proliferation to Gram (-) Bartonella bacilli in IMMUNOCOMPROMISED pts (HIV/transplant)
- benign lesion with red papules
- use Warthin Silver Stain to visualizes bacteria and treat with antibiotics
What is Kaposi Sarcoma and how does it progress physically?
- angioproliferative disorder caused by HHV-8 (double stranded) creating erythematous nodules
- starts as macule (dilated channels, small hyperchomatic nuclei) –> plaque (infiltrative spindle cells with irregular vascular channels) –> Tumor/Nodule (nodular spindle cell mass)
Kaposi Sarcoma
What is the difference between Classic, Endemic, Iatrogenic, and AIDS-associated forms?
C: sporadic, usually LE; indolent
- Mediterranean, Middle-Eastern, Eastern European M
E: African children < 10 yo; LN and cutaneous
I: T cell immunosuppression in transplant pts.
- Calcineurin
A: MOST COMMON IN US; disseminated/aggressive
- most common type of AIDS related malignancy
What is an Angiosarcoma and what are 3 risk factors related to the Liver development?
What are two other risk factors for development of angiosarcoma?
What is a common genetic marker of disease?
- malignant vascular tumor that is locally invasive and frequently metastasizes (poorly defined vessels lined by endothelial cells w/ATYPIA)
Liver: arsenic, thorotrast, and PVC production
- also arises from lymphadema w/axillary node dissection = lymphangiosarcoma; also RADIATION for carcinoma
check for CD31 and CD34 cells!
What is Balloon Angioplasty and Vascular Grafting?
BA: balloon that can compress plaque in vessels; used with stents (mesh wiring, usually drug-eluting) to help open up vasculature (drugs block thrombosis)
- balloons can cause plaque rupture
- stents can cause immediate thrombosis
VG: either synthetic or autologous; replacement of vessel or bypass of occluded vessel
- ONLY USED in LARGE VESSEL applications
- ex: Coronary Artery Graft or AAA stent graft
