Blood Vessels Flashcards
Localized abnormal dilation of a blood vessel or the heart?
– Not present at birth, but develop over time due to underlying defect in the MEDIA of the vessel
Aneurysms
– Arteriovenous shunting: arteries →veins WITHOUT intervening capillaries
– Tangle, WORM-like vascular channels with prominent pulsatile arteriovenous shunting with high blood flow
Arteriovenous malformations (AVM)
Large or multiple AVMs may shunt blood from arterial to venous circulation, which forces heart to pump additional volume leading to?
High-output cardiac failure
Focal irregular THICKENING in medium & large muscular arteries (renal, carotid, splanchnic, & vertebral vessels)
– Usually developmental defect, but can arise from TRAUMA etc
Fibromuscular dysplasia
Which type of aneurysms involve the circle of Willis and AD polycystic kidney?
Berry aneurysms
Which type of aneurysms involve “the worst headache I’ve ever had”?
Berry aneurysms
Facts on Berry aneurysms:
• ~?% of population has saccular aneurysms
• About ?% saccular found near major BRANCH points of the anterior circulation
- Most frequent cause of clinically significant ? is rupture of saccular (berry) aneurysm
- Aneurysms > ?mm in diameter ~ 50% risk of bleeding per year
- ~? of ruptures associated with acute increases in intracranial pressure
– Straining at stool or Sexual orgasm - ?% die with first rupture
- ? bleeding common in survivors
- 2%
- 90%
- subarachnoid
hemorrhage (SAH) - 10 mm
- 1/3
- 25-50%
- Repeat
Which type of aneurysms originate from:
1) embolization of a SEPTIC EMBOLUS, usually as a complication of INFECTIVE ENDOCARDITIS
2) an EXTENSION of an adjacent suppurative process
3) circulating organisms DIRECTLY INFECTING the arterial wall
Mycotic aneurysms
Which type of aneurysm bulges from one side of an artery. A neck leads to it?
Saccular (berry) aneurysm
Which type of aneurysm can involve more than one artery. It is over 2.5 cm wide?
Giant aneurysm
Which type of aneurysm bulges from all sides of an artery. It rarely has a neck?
Fusiform aneurysm
Which type of aneurysm bulges from all sides of an artery. It rarely has a neck?
Fusiform aneurysm
– can result from rupture of an arterial aneurysm into the adjacent vein
– penetrating injuries that pierce arteries & veins
– or from inflammatory necrosis of adjacent
vessels
Arteriovenous malformations (AVM)
AVM:
• surgically generated arteriovenous
fistulas provide vascular access for what?
chronic hemodialysis
Facts on Fibromuscular Dysplasia:
- Cause = ?
- ? degree relatives have ↑ incidence; especially common in ?
- Medial and intimal hyperplasia leads to ?
- ? due to fibromuscular dysplasia of RENAL arteries
- ? on angiography due to mkd attenuation of adjacent media
- Can develop aneurysms that may rupture
- unkn, probably developmental
- First; young women
- Luminal stenosis
- Renovascular HTN
- “string of beads”
What kind of cells have:
– Ability to proliferate
– synthesize collagen, elastin & proteoglycans
– Elaborate growth factors & cytokines
– Vasoconstriction &/or dilation
- Also involved with NL vascular repair and atherosclerosis
Vascular smooth muscle cells
What is the stereotypical response of a vessel wall to any insult?
Intimal thickening
Associated with endothelial cell dysfunction or loss, stimulates smooth muscle cell
recruitment and proliferation, and associated matrix synthesis
Intimal thickening
What type of cells are motile, undergo cell division, acquire new
biosynthetic capabilities?
Neointimal smooth muscle cells
The initial event following vascular injury is?
Endothelial cell activation
What is the basal state for endothelial cells?
Non-adhesive, non thrombogenic surface
What does the “activated state” for endothelial cells involve?
- Increased expression of procoagulants, adhesion molecules, and proinflammatory factors
- Altered expression of chemokines, cytokines, and growth factors
What brings about the activated state of endothelial cells?
- Turbulent flow
- HYPERTENSION
- Cytokines
- Complement
- Bacterial products
- LIPID PRODUCTS
- Advanced glycation end-products
- Hypoxia, acidosis
- Viruses
- CIGARETTE SMOKE
What are the steps for the response to vascular injury?
- Recruitment of smooth muscle cells or smooth muscle precursor cells to the intima
- Smooth muscle cell mitosis
- Elaboration of extracellular matrix
Hypertensive Vascular Disease
- Major risk factor in ?
- Sustained diastolic > ? mmHg or sustained systolic > ? mmHg are associated with increased risk of atherosclerosis
- 29% of population is hypertensive based on these numbers
- atherosclerosis
- 89
- 139
Which disease?
- underlying RENAL OR ADRENAL dz,
- ~5% of population
Secondary HTN
Which diseases are associated with Secondary HTN?
- Primary aldosteronism, Cushing syndrome, or pheochromacytoma
Secondary HTN:
- Hypertension secondary to ? is caused by increased production of RENIN from the ischemic kidney; a ? can be heard on auscultation of the affected kidneys
- renal artery stenosis
- bruit
Type of Hypertension that is idiopathic and involves 90-95% of the population?
Essential HTN
Essential HTN:
- Prevalence and vulnerability increases with ? and with which race?
- Age
- African - American
Complications of Essential HTN bring about?
- Cardiac hypertrophy and heart failure (hypertensive heart dz, HHD), multi-infarct dementia, and renal
failure
Essential HTN:
What do untreated HTN patients die of?
Half (1/2) die of ischemic heart dz (IHD) or congestive heart failure
- Another third (1/3) die of stroke
Which type of HTN involved with 5% of pop and rapid increase in BP and results in death within 1-2 years?
Malignant HTN (rare)
What is the systolic and diastolic for Malignant HTN?
- Systolic >200 mmHg
- Diastolic > 120 mmHg
What type of HTN involved with
– Severe HTN, renal failure, retinal hemorrhages & exudates +/- papilledema
– Often superimposed on pre-existing benign HTN
Malignant HTN
Table 11-1
Type of HTN that Accounts for 90% to 95% of all cases?
Essential HTN
Table 11-1
Causes of Renal Secondary HTN
•Acute glomerulonephritis •Chronic renal disease •Polycystic disease •Renal artery stenosis •Renal vasculitis •Renin-producing tumors
Table 11-1
Causes of Endocrine Secondary HTN
- Adrenocortical hyperfunction (Cushing syndrome, primary aldosteronism, congenital adrenal hyperplasia, licorice ingestion)
- Exogenous hormones (glucocorticoids, estrogen [including pregnancy-induced and oral contraceptives], sympathomimetics and tyramine-containing foods, monoamine oxidase inhibitors)
- Pheochromocytoma •Acromegaly •Hypothyroidism (myxedema) •Hyperthyroidism (thyrotoxicosis) •Pregnancy-induced
Table 11-1
Causes of Cardiovascular Secondary HTN?
- Coarctation of aorta •Polyarteritis nodosa •Increased intravascular volume •Increased cardiac output
- Rigidity of the aorta
Table 11-1
Causes of Neurologic Secondary HTN?
- Psychogenic
- Increased intracranial pressure
- Sleep apnea
- Acute stress, including surgery
BP is a function of?
- Both are influenced by multiple genetic and environmental factors
cardiac output & peripheral vascular resistance
Definition: Heart rate and stroke vol (which is strongly influenced by blood
volume which is regulated by renal sodium excretion or resorption)
Cardiac output
Definition:
regulated at level of arterioles; influenced by neural and hormonal inputs
Vascular resistance
Equation for BP
Cardiac Output X Peripheral Resistance
Cardiac output is affected by?
- Blood volume
- Sodium
- Mineralocorticoids
- Atrial natriuretic peptide - Cardiac factors
- Heart rate
- Contractility
Peripheral resistance is affected by?
1. Humoral factors A. Constrictors - Angiotensin II - Catecholamines - Thromboxane - Leukotrienes - Endothelin
B. Dilators
- Prostaglandins
- Kinins
- NO
- Neural Factors
A. Constrictors
- alpha- adrenergic
B. Dilators
- beta- adrenergic
- Local Factors
- Autoregulation
- pH, hypoxia
Blood Pressure Regulation
• Bld volume and vascular tone modified & maintained by ?
• In states of low volume or low peripheral resistance, or a decreased glomerular
filtration rate, ? is released by juxtaglomerular cells in the afferent arterioles
in the kidneys
• Renin cleaves circulating angiotensinogen to form ?
• Angiotensin I is cleaved to form angiotensin II by ACE (angiotensin- converting
enzyme)
- Angiotensin II is a potent but short-lived vasoconstrictor
- Angiotensin II also stimulates adrenal cortex to release ?, causing renal reabsorption of sodium and water
- Resistance and volume are increased, raising blood pressure
• The volume expansion induces myocardial release of ?,
leading to Na+ excretion and diuresis, as well as vasodilation—thus lowering blood pressure
•renin-angiotensin-
aldosterone system
- renin
- angiotensin I
- aldosterone
- atrial natriuretic peptide
HTN occasionally controlled by a ? gene DO, or is secondary to
? dz, ? dz, or other ? DO
- single
- renal, adrenal, other endocrine
Sustained HTN requires participation of the ?
kidney
HTN causes degenerative changes in the walls of large and medium arteries, that can lead to ?
Aortic dissection and/or cerebrovascular hemorrhage
What are 2 forms of small blood vessel bz?
- Hyaline arteriolosclerosis
2. Hyperplastic arteriolosclerosis
Homogeneous pink thickening and nephrosclerosis are associated with?
Hyaline arteriolosclerosis
Severe HTN, concentric lamellations (“onion skinning”), and necrotizing arteriolitis are associated with?
Hyperplastic arteriolosclerosis
What type of arteriolosclerosis?
- ↑smooth muscle matrix synthesis
- Plasma protein leakage across damaged endothelium
- Homogeneous pink (hyaline) thickening of the vessel wall, → luminal narrowing
- In nephrosclerosis due to chronic HTN, arteriolar narrowing of hyaline
arteriosclerosis → diffuse impairment of renal blood supply and glomerular scarring
Hyaline arteriolosclerosis
- Occurs in severe hypertension
- Smooth muscle cells form concentric lamellations (“onion skinning”) → luminal narrowing
- In malignant hypertension, laminations are accompanied by fibrinoid deposits and
vessel wall necrosis (necrotizing arteriolitis) , particularly in the kidney
Hyperplastic arteriolosclerosis
characterized by mild to moderate increase of blood pressure and an asymptomatic period of several years before the inevitable onset of symptoms and end-organ damage (hence, the condition is not truly benign).
Benign HTN
characterized by marked increase of blood pressure and rapid progression over a few weeks to end-organ failure.
Malignant HTN
Atherosclerosis underlies the pathogenesis of ?, ?, and ? vascular dz
coronary, cerebral, and peripheral vascular dz
Atherosclerosis:
• Extremely common, especially in the developed world
- “causes more morbidity and mortality (roughly ? of all deaths) in the Western world than any other disorder”
- ? responsible for almost ¼ of all deaths in US
- ? highest ischemic heart dz mortality; 3-5X US, 7-12X Japan
- half
- Myocardial infarction
- Soviet Union
Atherosclerosis:
• Prevalence and extent of disease is related to multiple risk factors,
which have ? (rather than additive) effect (see Table 11-2)
• 40-60yo incidence ↑?X; death rates from ischemic heart dz ↑each
decade
•? women are somewhat protected
– atheroprotective effect of ESTROGEN if started early postmenopausal, otherwise no benefit
•? is a major risk factor even in absence of other
factors, it is sufficient to initiate lesion development
• ? syndrome: assoc with central obesity
- INSULIN RESISTANCE, HTN, dyslipidemia (↑LDL, ↓HDL), HYPERCOAGULOBILITY, and pro-inflammatory state may contribute to endothelial dysfunction and/or thrombosis
- synergistic
- 5
- Premenopausal
- Hypercholesterolemia
- Metabolic Syndrome
Major Risk Factors for Atherosclerosis:
Nonmodifiable (Constitutional)/ HEREDITARY
- Between ages 40 and 60, incidence of MI increases five-fold
- Genetic abnormalities
- Family history
- Increasing age
- Male gender
Major Risk Factors for Atherosclerosis: Modifiable (ACQUIRED)
- Incidence of MI 2X as high in patients with DM than in those without
- Hyperlipidemia •Hypertension •Cigarette smoking •Diabetes
* Inflammation
What predicts cardiovascular risk?
C Reactive Protein (CRP)
Pathogenesis of Atherosclerosis:
What are the 2 types of endothelial injury and dysfunction?
- Hemodynamic turbulence
2. Circulating lipids
Pathogenesis of Atherosclerosis: Endothelial injury and dysfunction
Hemodynamic turbulence:
- Most lesions tend to occur at ?— due to flow disturbances normally seen in these locations
openings of exiting vessels, branch points, posterior
abdominal aorta
Pathogenesis of Atherosclerosis: Endothelial injury and dysfunction
Circulating lipids:
- Lipids in atheromatous plaques are predominantly cholesterol and cholesterol esters
- Accumulate in the ?, are taken up by macrophages and partially oxidized
- This modified LDL further accumulates within ? and ? cells,
forming ? cells and a lesion known as a ? - This stimulates an inflammatory response to accumulation of this toxic form of LDL
- intima
- macrophages
- smooth muscle
- foam
- “fatty streak”
Steps to the Arterial Response to Injury
- Chronic endothelial “injury”
- Hyperlipidemia
- Hypertension
- Smoking
- Homocysteine
- Hemodynamic factors
- Toxins
- Viruses
- Immune reactions - Endothelial dysfunction (e.g., increased permeability, leukocyte adhesion), monocyte adhesion and emigration
- Macrophage activation, smooth muscle recruitment **
- Macrophages and smooth muscle cells engulf lipid **
- Smooth muscle proliferation, collagen and other extracellular matrix deposition, extracellular lipid
Pathogenesis of Atherosclerosis: Inflammation
- Accumulation of cholesterol crystals within macrophages is recognized by the
inflammasome, which leads to ? secretion - More macrophages and ? are recruited and activated
- Inflammatory cytokines further activate endothelial cells, and growth factors stimulate
smooth muscle cells to migrate to the intima and proliferate
- IL-1
- T-lymphocytes
Pathogenesis of Atherosclerosis: Smooth muscle proliferation and matrix deposition
- Several growth factors are implicated in SMOOTH MUSCLE CELL PROLIFERATION, including ? (released by
locally adherent platelets) as well as macrophages, endothelial cells, and smooth muscle cells,?
growth factor, and ? - Proliferating smooth muscle cells synthesize extracellular matrix (ECM), including collagen
- Due to the intimal expansion from foam cells and extrace llular lipid, recruited inflammatory and smooth muscle cells and increased ECM, an ? is formed
- Over time, a soft fibrofatty plaque becomes cove red with a fibrous cap (dense collagen fibers). The center of the plaque is ?, containing lipid, debris, foam cells and
thrombus, SURROUNDED BY A ZONE OF INFLAMMATORY AND SMOOTH MUSCLE CELLS.
- PDGF
- fibroblast
- transforming growth factor-α (TGF- α)
- atheromatous plaque
- necrotic
Common sites of involvement for atherosclerosis in decreasing order of frequency/severity of involvement
- Abdominal aorta
- Coronary arteries
- Popliteal arteries
- Internal carotid arteries
- Circle of Willis
What are some complications of atherosclerotic plaques?
- Rupture and ulceration
- May lead to thrombosis - Hemorrhage
- May follow plaque rupture - Embolism
- May follow plaque rupture - Aneurysm formation
What are the consequences of atherosclerosis?
- Stenosis of the arterial lumen
2. Acute plaque change
How much has to be occluded to be considered critical stenosis?
70%
Consequences of atherosclerosis: Acute Plaque Change
- An acute thrombus may form over the plaque, occluding the artery. This may occur secondary to?
- Rupture of the plaque
2. Erosion or ulceration of the plaque surface
Emboli: may be composed of fat droplets, nitrogen bubbles, ? , tumor fragments, bone
marrow, or even foreign bodies. Emboli travel through the blood until
they encounter vessels too small to permit further passage, causing
partial or complete vascular occlusion.
atherosclerotic debris (cholesterol emboli)
“localized abnormal dilation of a blood vessel, or the heart,
that may be congenital or acquired”
Aneurysm
an INTACT (but thinned) muscular wall at the site of dilation
“True” aneurysm
DEFECT through the wall of the vessel, or heart, COMMUNICATING with an extravascular hematoma that
freely communicates with the intravascular space (“pulsating
hematoma”)
“False” aneurysm (pseudo-aneurysm)
• An ? arises when blood enters a defect in the arterial
wall and tunnels between its layers
arterial dissection
– Dissections are often, but not always, aneurysmal (see later)
– Both true and false aneurysms as well as dissections can rupture, often with
catastrophic consequences
An aneurysm may occur whenever the connective tissue of the
vascular wall is weakened, whether by acquired or congenital conditions:
- Defective vascular wall connective tissue
- ? syndrome (defective fibrillin synthesis), Ehlers-Danlos syndrome, scurvy… - Net degradation of vascular wall connective tissue
- Inflammatory conditions (such as atherosclerosis) lead to ↑ matrix metalloprotease (MMP) - Weakening of the vascular wall by ?
- ? → ischemia of inner media
- ? → ischemia of outer media
- ? → ischemia of outer media (thoracic aorta)
- Marfan
-
- ischemia
- Atherosclerosis
- Hypertension
- Tertiary syphilis
- Obliterative endarteritis (characteristic of late- stage syphilis) shows a predilection for small vessels, including those of the
vasa vasorum of the thoracic aorta. This leads to ischemic injury of the aortic media and aneurysmal dilation, which
sometimes involves the aortic valve annulus (aortic valve regurgitation).
Aneurysm:
Loss of vascular wall elastic tissue, or ineffective elastin synthesis, leads to ?, with disrupted and disorganized elastin filaments and increased ground substance (proteoglycans)
cystic medial degeneration
Aneurysm:
Cystic medial degeneration is a final common result of different conditions, including ? and ?
ischemic medial damage and Marfan syndrome
Aneurysm:
The two most important causes of aortic aneurysms are ?
atherosclerosis and hypertension
Aneurysm:
Mycotic aneurysms: can originate from?
– SEPTIC EMBOLI (usually complication of INFECTIVE ENDOCARDITIS)
– Extension of an adjacent SUPPURATIVE PROCESS
– CIRCULATING ORGANISMS DIRECTLY infecting the arterial wall
Abdominal Aortic Aneurysm (AAA):
Are typically due to ?
atherosclerosis
Abdominal Aortic Aneurysm (AAA):
Where do they occur?
Occur in the abdominal aorta, usually below the renal arteries, and often involve the common iliac arteries
Abdominal Aortic Aneurysm (AAA):
More frequent in?
- Men
- Smokers
- 6th decade of life
Abdominal Aortic Aneurysm (AAA):
- Characterized by severe atherosclerosis of the aorta, covered with ?
- May be detected as a ? mass in the abdomen
- mural thrombus
* pulsating
Abdominal Aortic Aneurysm (AAA):
Complications include?
- Rupture and hemorrhage
- Occlusion of branching arteries and downstream ischemia
- Embolism
- Impingement on another structure
Thoracic Aortic Aneurysm:
Often due to?
Often due to hypertension, or less commonly congenital
defect in connective tissue synthesis (Marfan)
Thoracic Aortic Aneurysm:
Clinical presentation is often due to?
◦ Impingement
- Lower respiratory tree
- Esophagus
- Recurrent laryngeal nerves
◦ Aortic valvular insufficiency
◦ Rupture
An autosomal dominant genetic disorder resulting in defective
synthesis of FIBRILLIN (FBN₁ that leads to aberrant TGF-β activity that weakens
elastic tissue
Marfan syndrome
Occurs when blood enters a defect in the intima and travels through a tissue plane within layers of the aortic media
Aortic Dissection
Aortic dissection occurs in?
- Hypertensive males, 40-60
- Younger patients with disorders of vessel connective tissue (Marfan)
Primary risk factor for aortic dissection is?
Hypertension
What is the classic presentation of an aortic dissection?
Sudden onset of severe chest pain (usually beginning in anterior chest), radiating to the back between the scapulae, & moving downward as the dissection progresses
– Can be confused with AMI
Aortic dissection pathogenesis:
- Blood enters aortic wall via an ? (cause generally unknown), forming an intramural hematoma
- Usually, in hypertensive patients, some degree of ?
- Most dissections arise in the ?, within 10cm of the aortic valve
- Dissections can rupture through the adventitia → massive hemorrhage (e.g., into the thoracic or abdominal cavities) or ? (hemorrhage into the pericardial sac)
• If the dissecting hematoma reenters the lumen of the aorta through a second distal intimal tear, a new false vascular channel (“?”) is created
– This averts a fatal extraaortic hemorrhage, and over time, such false channels can be
endothelialized to become recognizable ?.
- intimal tear
- cystic medial degeneration
- ascending aorta
- cardiac tamponade
• double-barreled aorta
- chronic dissections
Which type of dissections (involving the ascending aorta) are more common and associated with higher morbidity and mortality?
Type A
The most common cause of death (for both types A and B) is ?.
- Dissection may also extend along arterial branches of the aorta, causing potential occlusion of those vessels.
Rupture
How are Type A dissections treated?
Type A dissections are treated with antihypertensive therapy and an attempt to surgically repair the intimal tear.
Inflammation of vessels
Vasculitis
Vasculitis:
- Clinically depends on vascular bed affected (CNS vs heart vs small bowel)
- Constitutional symptoms?
fever, malaise, arthralgia’s, myalgias
Vasculitis:
Any type of vessel may be affected: more often ?
arterioles, capillaries &
venules affected (a few vasculitides tend to affect only one vessel type or
location)
What is the treatment for immune-mediated vasculitis?
Immunosuppressive treatment
? can also indirectly induce a noninfectious vasculitis
Infections
- Generating immune complexes or triggering cross-reactive immune response
? and ? injury can also cause vasculitis
Physical and chemical
- Irradiation, mechanical trauma, toxins,…
What is the major cause of noninfectious vasculitis?
Immune response (local or systemic)
Causes of Noninfectious Vasculitis
– Immune Complex-Assoc vasculitis
– Antineutrophil Cytoplasmic Antibodies
– Antiendothelial Cell Antibodies
– GIANT CELL (TEMPORAL) ARTERITIS ***
– Takayasu Arteritis
– POLYARTERITIS NODOSA (PAN) ***
– Kawasaki Dz
– Microscopic Polyangiitis
– Churg-Strauss Syndrome
– Behçet Disease
– GRANULOMATOSIS WITH POLYANGIITIS (FORMERLY WEGENER GRANULOMATOSIS) **
– THROMBOANGIITIS OBLITERANS (BUERGER DZ)
– Vasculitis Assoc with Other Noninfectious DOs
Primary forms of Vasculitis: Giant Cell Arteritis
What are some facts to know?
- Aorta is involved
- Eosinophils are very rare
- There are often giant cells but not required
- History: >40 year old +/- polymyalgia rheumatica
Primary forms of Vasculitis: Granulomatosis with Polyangiitis
Some facts to know?
Granulomas are required
Primary forms of Vasculitis: Churg-Strauss Syndrome
Some facts to know?
- Eosinophils are required
- Clinical history: Asthma, atopy
Primary forms of Vasculitis: Buerger Disease
Some facts to know?
- Thrombosis is required
- Clinical history: Young male smoker
Primary forms of Vasculitis: Behcet Disease
Some facts to know?
- Neutrophils are required
- Clinical history: Orogenital ulcers
- Autoantibody production and formation of immune complexes
- Deposition of ANTIGEN-ANTIBODY COMPLEXES in vascular walls
- Incites an inflammatory reaction within the wall
- Antigen is often unidentified
Noninfectious vasculitis: Immune Complex Vasculitis
Noninfectious vasculitis: Immune Complex Vasculitis
May be seen in?
- Systemic immunologic diseases (eg, SLE)
- Drug hypersensitivity
- Ex: PCN acts as a hapten binding to serum proteins of vessel wall- STREPTOKINASE acts as a foreign protein
- Clinical: mild to fatal; SKIN LESIONS most common
- Always consider DRUG HYPERSENSITIVITY! Stop drug –> resolution of vasculitis!!
- STREPTOKINASE acts as a foreign protein
- Secondary to exposure to infectious agent
- Ab to microbial constituents form immune complexes that deposit in vascular lesions
- POLYARTERITIS NODOSA : 30% assoc with HBsAg and anti-HBsAg
Noninfectious vasculitis:
What is a heterogeneous group of antibodies reactant with cytoplasmic
enzymes found in NEUTROPHIL granules, MONOCYTES, and endothelial cells?
Antineutrophil cytoplasmic antibodies (ANCA)
Noninfectious vasculitis: Antineutrophil cytoplasmic antibodies (ANCA)
What are the 2 types of ANCA and what are they associated with?
- Anti-proteinase-3 = PR3-ANCA (previously c-ANCA)
- Associated with POLYANGIITIS - Anti-myeloperoxidase = MPO-ANCA (previously p-ANCA)
- Induced by RX: propylthiouracil
- Associated with MICROSCOPIC POLYANGIITIS AND CHURG-STRAUSS SYNDROME
Noninfectious vasculitis: Antineutrophil cytoplasmic antibodies (ANCA)
- ANCA ? generally follow disease severity
- ANCAs activate ?, which then release reactive oxygen species
- “?” due to ANCA Ab directed against cellular constituents and do NOT form circulating immune complexes
- vascular lesions do not typically contain Ab and complement
- titers
- neutrophils
- pauci-immune
What is the most common vasculitis among OLDER patients and may present with constitutional symptoms (fever, fatigue, wt loss)?
Noninfectious vasculitis: Giant cell (temporal) arteritis and aortitis
What important symptoms are associated with Giant cell (temporal) arteritis & aortitis?
Facial pain and headache
Giant cell (temporal) arteritis and aortitis:
• Chronic (T cell mediated, CD4+ > CD8+) inflammation of arteries in the head, especially the ?
- Medial granulomatous inflammation, often with ? cells
- FRAGMENTATION OF THE ELASTIC LAMINA, AND INTIMAL THICKENING
- Sites of involvement within an artery may be ? and focal (at least 1cm bx)
- Healed sites of inflammation show scarring of the media and intimal thickening
- “double vision”, or involvement of the ? artery may lead to vision loss
• temporal arteries
- multinucleated giant
- patchy
- ophthalmic
Pulseless disease
Noninfectious Vasculitis: Takayasu arteritis
Noninfectious Vasculitis: Takayasu arteritis
Characterized by ? disturbances and marked weakening of pulses of the ? extremities
- ocular
- upper
What is an important symptom of Takayasu arteritis?
weak pulse and low blood pressure in the upper extremities (UE)
Noninfectious Vasculitis: Takayasu arteritis
-? vasculitis of medium and larger arteries
- Granulomatous
Noninfectious Vasculitis: Takayasu arteritis
Similar histologic findings as those seen in giant cell arteritis, except ?
• Involves the AORTIC ARCH (AORTITIS) AND MAJOR BRANCH VESSELS
- Occ aortitis causes dilation and aortic valve insufficiency
- PULMONARY ARTERY (involved in ½ the cases), CORONARY AND RENAL ARTERIES MAY be involved
- Younger age group (<50)
- Historically assoc with JAPANESE population, now global distribution
What are the initial and later symptoms of Takayasu arteritis?
Initially nonspecific (fatigue, wt loss, and fever.
Later vasc sx dominate: ↓Decreased BP, weak carotid and UE pulses, visual deficits, retinal hemorrhages, total blindness, and neuro deficits.
- Distal aorta SX: claudication of legs, pulm art leads to –> pulm HTN, coronary art –>MI, renal art –> systemic HTN. Quiescent stage after a few years permits long-term survival with visual and neuro deficits.
What are the most common causes of aortitis?
GCA and another inflammatory
disease (rheumatologic) known as Takayasu’s arteritis.
Noninfectious vasculitis: Polyarteritis nodosa (PAN)
- Systemic vasculitis, likely immune complex mediated
- Involves (decreasing order of frequency)
- RENAL vessels, heart, liver, ?
- PULMONARY VESSELS are spared
- GI tract
Noninfectious vasculitis: Polyarteritis nodosa (PAN)
- May affect any age group, but classically ?
- Almost 1/3 of patients have chronic ?
- ? therapy is usually effective
- ? necrotizing inflammation (neutrophils, eosinophils, lymphocytes and macrophages); predilection for BRANCH POINTS
- Ulcerations, infarcts, ischemic atrophy or hemorrhage may be first sign of dz
- Sites of inflammation are typically NOT circumferential
- young adult
- hepatitis B
- HBsAg - HBsAb complexes are found in the involved vessels
- Immunosuppressive
- Segmental Transmural
Noninfectious vasculitis: Polyarteritis nodosa (PAN)
• Inflamed vessel wall susceptible to… ?
- Thrombus formation/occlusion
- Aneurysm
- Rupture
What is the classic presentation of Polyarteritis nodosa (PAN)?
- Can involve some combination of RAPIDLY ACCELERATING HYPERTENSION due to renal artery involvement; ABDOMINAL PAIN AND BLOODY STOOLS caused by vascular gastrointestinal lesions; DIFFUSE MYALGIAS; AND PERIPHERAL NEURITIS, predominantly affecting MOTOR NERVES.
- RENAL involvement is often prominent and a major cause of mortality. Untreated, PAN is typically FATAL; however, immunosuppression can yield remissions or cures in 90% of cases.
Acute arteritis of infants and small children (80% ≤ 4 years)
Noninfectious Vasculitis: Kawasaki disease
Kawasaki Disease
• Often involves the ? arteries
- Affected sites may form aneurysms –> thrombosis or rupture –> ?
• Presenting picture is usually ? of the conjunctiva, oral mucosa, PALMS AND SOLES; desquamative rash
- cervical lymph node enlargement “?”
• Usually self-limited, but ? and ? are indicated to lower the risk of a coronary event
• coronary
- acute MI
• erythema
- “Mucocutaneous lymph node syndrome”
• IVIg and aspirin
What are the major symptoms of Kawasaki disease?
conjunctival and oral erythema and blistering, edema of the hands and feet, erythema of the palms and soles, desquamative rash, and cervical LN enlargement.
Necrotizing vasculitis involving arterioles, capillaries and venules
Noninfectious vasculitis: Microscopic polyangiitis
Unlike polyarteritis nodosa, all lesions of microscopic polyangiitis tend to be
of the SAME ? in any given patient and are distributed more widely
- Henoch-Schonlein purpura, essential mixed cryoglobinemia,
vasculitis assoc with CT DOs
age
What are the most common vessels of many organs systems that are affected by Microscopic polyangiitis?
Renal glomeruli and lung capillaries (90% necrotizing glomerulonephritis)
Most cases of Microscopic polyangiitis are associated with?
MPO-ANCA
Noninfectious vasculitis: Microscopic polyangiitis
• Segmental necrotizing inflammation with ?
- Many ? neutrophils are usually seen
- ”? vasculitis” or “? vasculitis”
• fibrinoid necrosis
- apoptotic
- leukocytoclastic vasculitis” or “hypersensitivity vasculitis”
Noninfectious vasculitis: Microscopic polyangiitis
- ? induces remission, markedly im proves long- term survival
- Immunosuppression
What are the symptoms of Microscopic polyangiitis?
Major clinical features include hemoptysis, hematuria and proteinuria, bowel
Fragmented PMNs
pain or bleeding, muscle pain or weakness, and palpable cutaneous purpura.
allergic granulomatosis and angiitis
Churg-Strauss syndrome
Noninfectious vasculitis: Churg-Strauss syndrome
Small vessel necrotizing vasculitis, associated with?
ASTHMA, ALLERGIC RHINITIS, HYPEREOSINOPHILIA, lung infiltrates, extravascular granulomas
Noninfectious vasculitis: Churg-Strauss syndrome
- The inflammation may resemble PAN or microscopic polyangiitis, with the addition
of ? and ? - Less than 1/2 show ? positivity
- eosinophils and granulomas
- ANCA positivity (MPO-ANCA mostly)
Noninfectious vasculitis: Churg-Strauss syndrome
What organ systems are involved?
Multisystem diseases with cutaneous involvement (PALPABLE PURPURA), GI TRACT BLEEDING, and RENAL DISEASE (primarily as focal and segmental glomerulosclerosis)
Noninfectious vasculitis: Churg-Strauss syndrome
- Myocardial involvement may give rise to ?; heart is involved in 60%
of patients, and accounts for almost HALF OF THE DEATHS in the syndrome
- cardiomyopathy
Vasculitis of small - medium vessels with classic triad SX
Behçet disease
What is the classic triad of Behçet disease?
- Aphthous ulcers of the oral cavity
- Genital ulcers
- Uveitis
- Also GI and pulmonary manifestations
What gene is associated with Behçet disease?
HLA-B51
Noninfectious vasculitis: Behçet disease
- The vessel inflammation is ? and morphologically nonspecific, may involve visceral organ systems with subsequent aneurysm formation
- Disease mortality related to severe ? or ?
- neutrophilic
- neurologic involvement or rupture of aneurysms
What is the treatment for Behçet disease?
Immunosuppression with steroid or TNF-antagonist tx effective
Formerly known as Wegener granulomatosis
Noninfectious Vasculitis: Granulomatosis with polyangiitis
Noninfectious Vasculitis: Granulomatosis with polyangiitis
Necrotizing vasculitis featuring?
- NECROTIZING GRANULOMAS of the upper and/or lower respiratory tracts
- NECROTIZING OR GRANULOMATOUS VASCULITIS, most prominently in the respiratory tract
- Focal necrotizing, often CRESCENTIC, glomerulonephritis (remember this for renal!) *****
What is Granulomatosis with polyangiitis associated with in up to 95% of cases?
PR3-ANCA
Noninfectious Vasculitis: Granulomatosis with polyangiitis
a form of ? hypersensitivity response to normally “innocuous” inhaled
microbial or other environmental agents
T-cell–mediated
What gender and age are associated with Granulomatosis with polyangiitis?
M > F, Avg age of 40
What symptoms are associated with Granulomatosis with polyangiitis?
Persistent pneumonitis & sinusitis, renal disease, and nasopharyngeal ulceration ***
- Rashes, myalgias, articular involvement, neural inflammation and fever
Why is Granulomatosis with polyangiitis dangerous?
• Left untreated, rapidly fatal, 80% mortality at one year
- Once fatal , now CHRONIC RELAPSING AND REMITTING
What is the treatment for Granulomatosis with polyangiitis?
steroids, cyclophosphamide, TNF antagonists
Noninfectious Vasculitis: Granulomatosis with polyangiitis
Morphology:
– Upper respiratory tract: sinonasal and pharyngeal inflammation with
granulomas and vasculitis (granulomas with ? and accompanying vasculitis)
– Lower respiratory tract: multiple necrotizing granulomas, which may coalesce and ?
- geographic patterns of central necrosis
- cavitate
• SEGMENTAL, THROMBOSING, acute and chronic vasculitis of small and medium vessels,
especially
- TIBIAL arteries and RADIAL arteries
- Occ secondary extension to VEINS AND NERVES of the extremities (leading to pain)
- May lead to vascular insufficiency of the extremities
- Chronic ulcerations, which may lead to gangrene
Noninfectious vasculitis: Thromboangiitis obliterans (Buerger disease)
What type of patients are typically associated with Thromboangiitis obliterans (Buerger disease)?
• Patients are almost always HEAVY SMOKERS, <35 yo
- Most have hypersensitivity to intradermally injected tobacco products
- Assoc with HLA haplotypes of certain ethnic grps: Israeli, Indian subcontinent and Japanese
Noninfectious vasculitis: Thromboangiitis obliterans (Buerger disease)
Acute and chronic inflammation, accompanied by luminal thrombosis. Thrombus can contain small ? composed of neutrophils surrounded by granulomatous inflammation.
microabscesses
What symptoms are associated with Thromboangiitis obliterans (Buerger disease)?
Early manifestations cold-induced RAYNAUD PHENOMENON, leg pain induced by exercise that is relieved on rest (INTERMITTENT CLAUDICATION), instep foot pain induced by exercise (INSTEP CLAUDICATION), and a SUPERFICIAL NODULAR PHLEBITIS (venous inflammation). Vascular insufficiency tends to be accompanied by SEVERE PAIN—EVEN AT REST— undoubtedly due to the neural involvement. CHRONIC EXTREMITY ULCERATIONS DEVELOP, progressing over time (occasionally precipitously) to FRANK GANGRENE.
Infectious Vasculitis involves direct invasion of what infectious agents?
– Pseudomonas
– Aspergillus
– Mucor
What kind of aneurysms are involved with Infectious Vasculitis?
Mycotic aneurysms
Infectious Vasculitis:
• Vascular invasion as part of a localized tissue infection, or less commonly ? spread
- Septicemia or embolization from infective endocarditis
• hematogenous
Excessive vasospasm of small arteries and arterioles, especially FINGERS AND TOES
Raynaud Phenomenon
“red white and blue”
Facts about Primary Raynaud phenomenon (previously known as Raynaud DZ)?
- Induced by COLD or EMOTION; symmetric involvement of the digits
- Estimated 3-5% general population; YOUNG WOMEN
- BENIGN course
Facts about Secondary Raynaud phenomenon?
• A component of another arterial disease such as SLE, SCLERODERMA, or thromboangiitis
obliterans; ASYMMETRIC involvement of digits
• WORSENS WITH TIME
Excessive vasoconstriction of myocardial arteries or arterioles (“cardiac Raynaud”)
may cause ischemia or infarct
Myocardial vessel vasospasm
Myocardial vessel vasospasm:
High levels of vasoactive mediators can precipitate prolonged myocardial vessel
contraction
- Usually caused by circulating vasoactive agents, which may be endogenous
(?), or exogenous (?)
endogenous
epinephrine, pheochromocytoma), or exogenous (cocaine
What is the outcome of myocardial vessel vasospasm?
Sudden cardiac death or Takotsubo cardiomyopathy: “broken heart syndrome”, associated with emotional duress
For Varicose veins, embolism from thrombi of ? lower extremity veins is rare
• As opposed to deep vein thrombosis (DVT)
superficial
• Esophageal varices
– PORTAL HYPERTENSION (often due to cirrhosis) opens portosystemic shunts which direct blood to veins at the gastroesophageal junction such as?
- Esophageal varices (clinically important because they may fatally rupture)
- rectum (hemorrhoids)
- Periumbilical veins (Caput medusa)
Dilation of the venous plexus at the anorectal junction
Hemorrhoids
Single most important risk factor for developing a deep venous thrombosis (DVT) in the LE is?
What can also increase the risk of DVT?
- prolonged inactivity/immobilization
- Systemic hypercoagulability may also increase risk of DVT
What is the most serious potential consequence of Thrombophlebitis?
Pulmonary embolism
Migratory thrombophlebitis (Trousseau sign):
- Patients with cancer may experience ? as a paraneoplastic syndrome
- Particularly seen with ?
• In the classic case, venous thromboses appear at one site, disappear, and reappear at a
different site
• Associated with adenocarcinomas of the ?, ?, ?
• hypercoagulability
• mucin-producing adenocarcinomas (mucin is thought to be
thrombogenic )
• lung, ovary, pancreas
What clinical issue arises with Superior vena cava syndrome?
• obstruction produces a characteristic clinical complex:
- MARKED DILATION OF THE VEINS OF THE HEAD, NECK, AND ARMS WITH CYANOSIS
- Pulmonary vessels can also be compressed –> RESPIRATORY DISTRESS
Disease where neoplasms compress or invade the SVC?
- bronchogenic carcinoma, mediastinal lymphoma, or aortic aneurysm
Superior vena cava syndrome
Neoplasms that compress or invade the IVC; or thrombosis of the hepatic, renal, or
lower extremity veins that propagates cephalad
Inferior vena cava syndrome
How can Inferior vena cava syndrome occur?
Hepatocellular Carcinoma (HCC) and Renal Cell Carcinoma (RCC): tend to grow within veins, can ultimately occlude the IVC, and extend into the right atrium
Clinical issues with Inferior vena cava syndrome?
• IVC obstruction induces marked lower extremity edema, distention of the superficial
collateral veins of the lower abdomen
- renal vein involvement –> massive proteinuria
Acute inflammation and spread of bacterial infection into lymphatics
Lymphangitis
What is the most common agent for Lymphangitis?
group A beta-hemolytic streptococci
isolated congenital defect, of familial Milroy disease
lymphatic agenesis or hypoplasia
Primary Lymphedema
Blockage of previously normal lymphatic
Secondary or obstructive lymphedema
Secondary or obstructive lymphedema can be due to?
Malignant tumor, surgical procedures (radical mastectomy with axillary node dissection), post-irradiation fibrosis, filariasis, post inflammatory thrombosis or scarring
What is an example of Secondary or obstructive lymphedema?
peau d ‘ orange (orange peel): skin overlying breast cancer, draining lymphatics clogged
with tumor cells
List some Benign Neoplasms, Developmental and Acquired Conditions
• Hemangioma
- Capillary hemangioma
- Cavernous hemangioma
- Pyogenic granuloma
•Lymphangioma
- Simple (capillary) lymphangioma
- Cavernous lymphangioma (cystic hygroma)
•Glomus tumor
•Vascular ectasias
- Nevus flammeus
- Spider telangiectasia (arterial spider)
- Hereditary hemorrhagic telangiectasis (Osler-Weber-Rendu disease)
•Reactive vascular proliferations
- Bacillary angiomatosis
List some Intermediate-Grade Neoplasms
- Kaposi sarcoma
* Hemangioendothelioma
List some Malignant Neoplasms
- Angiosarcoma
* Hemangiopericytoma
a permanent dilation of preexisting small vessels (capillaries, venules, and
arterioles) that form a discrete red lesion—usually in the skin or mucous membranes. These can be congenital or acquired and are NOT TRUE NEOPLASMS; some of them are malformations and
others are hamartomas
Telangiectasia
(“birthmark”) most common form of vascular ectasia; light pink to deep purple flat lesion on the head or neck composed of dilated vessels. Most ultimately regress spontaneously.
Nevus flammeus
special form of nevus flammeus. Grow during childhood, thicken the skin surface, and do not fade with time. Such lesions in the distribution of the trigeminal nerve are associated with the STURGE-WEBER SYNDROME (aka: encephalotrigeminal angiomatosis ).
This uncommon congenital disorder is associated with FACIAL PORT WINE NEVI, IPSILATERAL VENOUS ANGIOMAS IN THE CORTICAL LEPTOMENINGES, MENTAL RETARDATION, SEIZURES, HEMIPLEGIA, AND SKULL RADIO-OPACITIES. Thus, a large facial telangiectasia in a child with mental
deficiency may indicate the presence of additional vascular malformations.
port wine stain
Autosomal dominant
disorder caused by mutations in genes that encode components of the TGF- beta signaling
pathway. The telangiectasias are malformations composed of dilated capillaries and veins
that are present at birth. They are widely distributed over the SKIN AND ORAL MUCOUS
MEMBRANES, as well as in the RESPIRATORY, GASTROINTESTINAL, AND URINARY TRACTS. The lesions can spontaneously rupture, causing serious epistaxis (nosebleed), gastrointestinal bleeding, or hematuria.
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease)
common tumors; localized increase in neoplastic blood vessels
Hemangiomas
What is the most common benign vascular tumor?
Capillary hemangioma
- Irregular, dilated vascular channels making a lesion with an indistinct border
- More likely to involve deep tissue, more likely to bleed
Cavernous hemangioma
- Type of capillary hemangioma (not pyogenic, not a granuloma)
- Rapidly growing, often in oral mucosa (may ulcerate); 1/4 dev following trauma
- Granuloma gravidarum (pregnancy tumor): gingiva of pregnant women
Pyogenic granuloma (lobular capillary hemangioma)
What type of lymphangiomas:
- Appear very similar to capillary hemangiomas, but without RBCs
- Subcutis of head/neck and axillae
Simple lymphangioma
Cavernous lymphangioma (cystic hygroma)
- Neck or axilla of children
- Can be large (up to 15 cm)
- Large cavernous lymphangiomas of the neck are often seen in ?
turner syndrome
– Benign tumors arising from glomus bodies, and most often appear in distal fingers
– Of SMOOTH MUSCLE origin rather than endothelial
– PAINFUL
Glomus tumor
Benign Vascular Tumors:
A vascular proliferation in response to gram negative Bartonella bacilli
Bacillary angiomatosis
Bacillary angiomatosis
• Occurs on the skin of ? patients
- The lesions are localized, forming ?
- Micro: PROLIFERATION OF CAPILLARIES WITH PLUMP ENDOTHELIAL CELLS
- The bacteria can be identified with PCR, or visualized with a
? stain - ? antibiotics are effective
• immunocompromised
- red papules
- Warthin-Starry
- Macrolide
Condition where:
– neoplastic endothelial cells are plump and cuboidal, resembling epithelium. Vascular channels may be difficult to recognize.
– variable clinical behavior, with metastasis in 20-30%
Epithelioid hemangioendothelioma
Disease caused by human herpesvirus 8 (HHV8)
Kaposi Sarcoma (KS)
What are 4 distinct clinical forms of Kaposi Sarcoma (KS)?
- AIDS-associated KS
- Classic KS
- Endemic African KS
- Transplant-associated KS
What is the most common form of Kaposi Sarcoma seen in the US and the MOST COMMON AIDS RELATED MALIGNANT TUMOR?
AIDS-associated KS
Which form of Kaposi Sarcoma is in Older men from Middle Eastern, Mediterranean or Eastern European descent.
NOT associated with HIV. Tumors localized to skin.
Classic KS
Which form of Kaposi Sarcoma is NOT associated with HIV. Patients < 40. Can involve lymph nodes.
Endemic African KS
Which form of Kaposi Sarcoma is NOT associated with HIV, but with T-cell immunosuppression. Can spread to lymph nodes and viscera
Transplant-associated KS
Malignant endothelial tumor
Angiosarcoma
Angiosarcoma:
• Age and gender?
• Can be induced by ? exposure; can arise in setting of lymphedema
(upper extremity after radical mastectomy)
-? angiosarcoma assoc with arsenic, pesticides, Thorotrast (contrast agent),
polyvinyl chloride
- May occur anywhere, but the most common sites: ?
- Locally invasive and may metastasize
- ? year survival around 30%
• Age: older; M = F
• radiation
- Hepatic
- Skin, Soft tissue, Breast and Liver
- 5 year
Vascular Replacement:
Synthetic large bore works for aorta, but small bore fail. Why do they hail and what do you end up using?
- small bore fail due to
thrombosis or intimal hyperplasia at junction of the graft with the native vasculature - Thus, utilize saphenous vein or left internal mammary arteries for small bore grafts (coronary arteries)
