Chapter 11: Vascular Anomalies, HTN, Atherosclerosis, Aneurysms/Dissections Flashcards
1
Q
In which layer of vessels will you find nerve fibers and the vasa vasorum (“vessels of the vessels”)?
A
Adventitia
2
Q
Which type of vessel has an endothelial cell lining, no media, and variable number of pericytes?
A
Capillaries
3
Q
In most inflammatory rxns, vascular leakage and leukocyte exudation occur via what vessels?
A
Post-capillary venules (veins)
4
Q
All vessels except _______ share a 3-layered architecture consisting of an endothelium lined intima, a surrounding smooth m. media, and supportive adventititia.
A
Capillaries
5
Q
Large or multiple AV fistulas may shunt blood from arterial or venous circulation, forcing the heart to pump additional volume and lead to what clinically significant event?
A
High-output cardiac failure
6
Q
Fibromuscular dysplasia is a focal thickening in which arteries (size and type)?
A
Medium and large muscular arteries (i.e, renal, carotid, splanchnic, and vertebral)
7
Q
Is there a genetic association with fibromuscular dysplasia and who is most often affected?
A
- First-degree relatives have ↑ incidence
- Most frequently in young women (NO assoc. w/ OC’s or ↑ estrogen)
8
Q
Which layers of the vessel wall undergo hyperplasia and fibrosis in fibromuscular dysplasia?
A
Media and intima
9
Q
Fibromuscular dysplasia of renal arteries can be a cause of?
A
Renovascular HTN
10
Q
Endothelial dysfunction refers to an alteration in endothelial what?
Often has what 2 characteristics?
A
- Phenotype
- Often both proinflammatory and prothrombogenic
11
Q
Alteration of endothelial phenotype seen in endothelial dysfunction is responsible for the initiation of what changes seen in pathological processes?
A
Initiation of thrombus formation, atherosclerosis, and vascular lesions of HTN
12
Q
Vascular smooth m. cells have the capacity to proliferate when appropriately stimulated and can also synthesize what?
A
- Collagen
- Elastin
- Proteoglycans
- Elaborate cytokines and GF’s
13
Q
What is the stereotypical response of the vessel wall to any insult?
A
Intimal thickening
14
Q
Turbulent flow, HTN, cytokines, complement, bacterial/lipid prods., advanced glycation end-products, hypoxia, acidosis, viruses and cigarette smoke may cause endothelial activation which leads to increased/altered expression of what?
A
- Procoagulants, adhesion molecules, and pro-inflammatory cytokines
- Altered expression of chemokines, cytokines, and GF’s
15
Q
Describe the 3 events in the stereotypical response to vascular injury.
A
- Recruitment of smooth m. cells or smooth m. precursor cells to intima
- Smooth m. cell mitosis
- Elaboration of extracellular matrix = intimal thickening
16
Q
Secondary HTN is a result of an underlying disease in which organs?
A
- Renal –> renal a. stenosis
- Adrenal = 1’ aldosteronism, Cushing syndrome or pheochromocytoma, pregnancy induced
- CV = coarctation of aorta, polyarteritis nodosa
- Neuro = sleep apnea, acute stress, psychogenic
17
Q
Which systolic and diastolic BP characterize malignant HTN?
A
>200/>120
18
Q
Malignant HTN is often superimposed on what?
A
Pre-existing “benign” HTN
19
Q
What are 5 cardiovascular causes of secondary HTN?
A
- Coarctation of aorta
- Polyarteritis nodosa
- Increased intravascular volume
- Increased cardiac output
- Rigidity of aorta
20
Q
What are 4 neurologic causes of secondary HTN?
A
- Sleep apnea
- ↑ ICP
- Sleep apnea
- Acute stress, including surgery
21
Q
Blood pressure is a product of _______ x________
A
Cardiac output x Peripheral Resistance
22
Q
The most important determinant of stroke volume is what?
Regulated by?
A
- Filling pressure
- Regulated thru Na+ homeostasis (mineralocorticoids and ANP) and its effect on blood volume
23
Q
How is cardiac output calculated?
A
CO = SV x HR
24
Q
List the 5 humoral factors which are constrictors and have an effect on peripheral resistance?
A
- Angiotensin II
- Catecholamines
- Thromboxane
- Leukotrienes
- Endothelin
25
Peripheral resistance is regulated predominantly at the level of which vessels?
By which inputs?
- **Arterioles**
- **Neural** and **hormonal** inputs
26
What 2 relaxing substances are produced by the kidney to counterbalance the vasopressor effects of angiotensin?
- NO
- Prostaglandins
27
Explain the effects of renal artery stenosis and how they contribute to renovascular HTN?
- ↓ pressure in afferent arteriole = ↓ GFR
- ↑ Renin secretion = RAAS system activation = ↑ vascular tone and blood volume
28
Liddle syndrome is due to gain-of-function mutations in which protein and leads to what?
- **ENaC** protein
- Causes ↑ Na+ reabsorption in response to **aldosterone**
29
Gene defects in which enzymes involved in aldosterone metabolism lead to primary hyperaldosteronism and in turn secondary HTN?
- Aldosterone synthase
- 11β-hydroxylase
- 17α-hydroxylase
30
HTN is associated with what 2 forms of small blood vessel disease?
1) Hyaline arteriolosclerosis
2) Hyperplastic arteriosclerosis
31
Homogenous pink hyaline thickening with associated luminal narrowing is characteristic of?
**Hyaline** arteriosclerosis
32
What type of arteriosclerosis is associated with severe HTN and is often a component of malignant HTN?
**Hyperplastic** arteriosclerosis
33
Vessels exhibiting concentric, **laminated ("onion-skin")** thickening of the walls with luminal narrowing is characteristic of?
**Hyperplastic** arteriosclerosis
34
Nephrosclerosis due to chronic HTN is a form of what type of arteriosclerosis?
Hyaline arteriosclerosis
35
What type of arteriosclerosis is a common feature of diabetic microangiography?
Hyaline arteriosclerosis
36
The laminations of hyperplastic arteriosclerosis are accompanied by what other morphological changes in malignant HTN?
- **Fibrinoid** deposits
- Vessel wall necrosis (**necrotizing arteriolitis**)
37
What do the laminations of hyperplastic arteriosclerosis consist of?
Smooth muscle cells w/ **reduplicated** BM
38
Monckeberg medial sclerosis most often occurs in which age group and is characterized by what?
Clinically significant?
- **\>50 yo**
- **Calcification** of walls of **muscular arteries**, typically **internal elastic membrane**
- **No** narrowing of lumen and **no** clinical significance
39
What is the most frequent and clinically important pattern of arteriosclerosis?
Atherosclerosis
40
The likelihood of atherosclerosis is determined by the combination of which acquired and inherited risk factors?
- **Acquired** = cholesterol levels, smoking and HTN
- **Inherited** = LDL receptor gene mutations
41
What are in the intimal lesions seen in atherosclerosis and describe their morphology?
- Atheroma = atheromatous = atherosclerotic plaque
- **Raised** lesion w/ a **soft grumous core** of lipid covered by **fibrous cap**
42
Besides obstructing blood flow, atherosclerotic plaques can rupture leading to what?
Catastrophic obstructive vascular **thrombosis**
43
Which country is known to have the highest ischemic heart disease-associated mortality?
Soviet Union
44
What are the 5 major modifiable risk factors for atherosclerosis?
1. Hyperlipidemia
2. HTN
3. Cigarette smoking
4. Diabetes
5. Inflammation
45
How do multiple risk factors present act in concert to increase risk of atherosclerosis?
Have a **multiplicative effect** = **Synergism**
46
Woman of which age are somewhat protected from atherosclerosis?
May due to effect of?
- Pre-menopausal woman
- Effect of **estrogen**
47
Atheroprotective effects of estrogen therpay seem to be related to what factor?
**Age** at which therapy is initiated --\> younger postmenopausal woman are **more** protected
48
What is a major risk factor for atherosclerosis even in the absence of other factors and is **sufficient** to initiate lesion development?
Hyper**cholesterolemia**
49
What are 2 activities which raise HDL levels?
- Exercise
- Moderate consumption of ethanol
50
Which disease causes a 100x ↑ risk for atherosclerosis-induced gangrene of LE's?
Diabetes mellitus
51
Which circulating marker of inflammation associated wth ischemic heart disease is one of the easiest to measure and one of the most sensitive?
CRP
52
Expression of CRP is increased by a number of inflammatory mediators, especially what?
IL-6
53
What is a useful serum marker to gauge the effects of risk reduction measures, such as smoking cessation, weight loss, exercise, and statins?
CRP
54
Serum homocysteine levels correlate with risk for what 4 vascular pathologies?
- Coronary atherosclerosis
- Peripheral vascular disease
- Stroke
- Venous thrombosis
55
Metabolic syndrome associated with central obesity is characterized by what dysfunctions?
- Insulin resistance
- HTN
- Dyslipidemia
- Hypercoagulability
- Pro-inflammatory state
56
The systemic hypercoagulable and proinflammatory state associated with metabolic syndrome contribute to what 2 pathological processes?
- Endothelial dysfunction
- Thrombosis
57
What is lipoprotein A [Lp(a)]?
Increases risk for what?
- **Altered** form of **LDL** --\> contains **ApoB-100** portion of LDL linked to **ApoA**
- Associated w/ **coronary** and **cerebrovascular disease** risk, independent of total cholesterol or LDL levels
58
Elevated plasminogen activator inhibitor 1 is a potent predictor of?
Risk for **major** atherosclerotic events, including MI and stroke
59
What are the 2 most important causes of endothelial dysfunction leading to atherosclerosis?
1. Hemodynamic disturbances = **turbulence**
2. Hypercholesterolemia
60
Where do plaques seen in atherogenesis most commonly occur?
- Openings of exiting vessles
- Branch points
- **Posterior** wall of the aorta
61
Which genetic disorder is associated with defective LDL receptors and inadequate hepatic LDL uptake which can precipitate MI before the age of 20?
Familial hypercholesterolemia
62
Chronic hypercholesterolemia can directly impair endothelial cell function by increasing the production of what?
**ROS** = membrane/mitochondrial damage + accelerated NO decay
63
With chronic hyperlipidemia, lipoproteins accumulate where in the vessel and undergo what?
- **Intima**
- Aggregate and are **oxidized** by **free radicals** --\> **modified LDL**
64
What occurs to the modified LDL that aggregates in the intima of vessels?
- Phagocytosed and accumulates in **macrophages** = **FOAM CELLS**
- Smooth m. cells can also transform into **lipid-laden foam cells**
65
What is the lesion caused by the accumulation of foam cells in the intima of vessels called?
Stimulates what?
- **Fatty streak**
- ***Lead to ↑ cytokine, ↑ GFs and ↑monocyte recruitment + activation***
66
Chronic inflammation which contributes to the initiation and progression of atherosclerotic lesions is triggered by what?
Leads to activation of the inflammasome and secretion of what?
- Accumulation of **cholesterol crystals** and **FFA's** in **macrophages**
- Secretion of **IL-1**
67
Secretion of IL-1 assoc. w/ chronic inflammation in atherosclerotic lesions leads to the recruitment and activation of what?
**More macrophages** + **T lymphocytes** = ↑ cytokines/chemokines which recruit and activate more inflammatory cells
68
Intimal smooth m. cell proliferation + extracellular matrix deposition convert fatty streaks into what?
**Mature atheroma**
69
Which GF's are implicated in smooth muscle proliferation associated w/ atherogenesis?
- PDGF
- FGF
- TGF-α
70
Smooth m. cells stimulated by GF's in atherogenesis synthesize what that stabilizes atherosclerotic plaques?
Extracellular matrix (notably **collagen**)
71
Atheromas are dynamic lesions consisting of what 4 cell types?
1. Dysfunctional endothelial cells
2. Proliferating smooth m. cells
3. T lymphocytes
4. Macrophages
72
Fatty streaks are a normal finding in which subset of pts?
- Aorta of infants
- Virtually all adolescents
73
How do atherosclerotic plaques appear grossly inside of a vessel?
- White, yellow and **patchy**, only portion of wall involved
- Eccentric appearance
74
In descending order of frequency/severity of involvement list the 5 vessels most extensively affected by atherosclerotic plaques.
1. Lower abdominal aorta
2. Coronary arteries
3. Popliteal arteries
4. Internal carotid arteries
5. Vessels of circle of Willis
75
The extracellular matrix of atherosclerotic plaques consist of what 3 components?
- Collagen
- Elastic fibers
- Proteoglycans
76
What is found deep to the fibrous cap of atherosclerotic plaques?
- **Necrotic core** containing lipids (primarily cholesterol and cholesterol esters)
- Debris from dead cells + Foam cells + Fibrin
77
What is seen morphologically at the periphery of atherosclerotic plaques?
- **Neovascularization**
- May also see **calcification** over time
78
Rupture, ulceration or erosion of the surface of atherosclerotic plaques exposes what and leads to?
- Exposes highly **thrombogenic** substances
- Leads to **thrombosis**
79
Rupture of the overlying fibrous cap, or of the thin-walled vessels in the area of neovascularization of atherosclerotic plaques can lead to what?
- **Hemorrhage** into the plaque (**intraplaque hemorrhage**)
- Contained **hematoma** may expand the plaque or **induce plaque rupture**
80
Atherosclerotic plaque rupture can discharge atherosclerotic debris where and lead to what?
- Into the bloodstream
- Producing **micoemboli**
81
Atherosclerosis-induced pressure or ischemic atrophy of the underlying media, with loss of elastic tissue, causes weakness and potential rupture due to formation of a?
Aneurysm
82
What are the 4 major "downstream" consequences of atherosclerosis?
1. MI (heart attack)
2. Cerebral infarction (stroke)
3. Aortic aneurysms
4. Peripheral vascular disease (gangrene of the legs)
83
The stage at which occlusion of a vessel is sufficiently severe to produce ischemia is known as?
Critical stenosis
84
What % decrease in luminal cross-section area is considered critical stenosis?
70%
85
Critical stenosis of the arterial lumen may lead to chronic ischemia in which parts of the body?
- Myocardium
- Bowel (mesenteric ischemia)
- Brain (ischemic encephalopathy)
- Extremities (intermittent claudication)
86
Critical stenosis of the coronary artery can lead to chest pain w/ exertion, known as?
Stable angina
87
Acute plaque change falls into what 3 general categories?
1. **Rupture/fissuring**
2. **Erosion/ulceration**
3. **Hemorrhage into the atheroma**
88
What are the characteristics of "vulnerable plaques" in terms of the fibrous cap, foams cells, and smooth m. cells?
- Contain **large** **areas** of **foam cells**/extracellular l**ipids**
- **THIN fibrous caps**
- **Few** smooth m. cells + **dense** **clusters** of **inflammatory cells**
89
What is the major structural component of the fibrous caps of atherosclerotic plaques and what produces this structural component?
- **Collage****n**
- Produced by **smooth m. cells**
90
What are 2 influences extrinsic to plaques which contribute to acute plaque change?
- **Adrenergic stimulation**: ↑ BP + ↑ vasoconstriction= ↑ stress on plaque ---\> seen with **wakening** and **rising** in the AM
- **Intense emotional stress**: ↑ BP = ↑ stress on plaque
91
**Spherical** outpouchings involving **only a portion** of the vessel wall describes what type of aneurysm?
Saccular
92
**Diffuse**, **circumferential** dilation of **long** vascular **segments** defines what type of aneurysm?
Fusiform aneurysms
93
**Defect** in the vascular wall leading to an **extravascular hematoma** that **freely communicates** with the intravascular space ("pulsating hematoma") defines what?
False aneurysm (aka pseudo-aneurysm)
94
Defective synthesis of the scaffolding protein *fibrillin* leading to aberrant TGF-β activity and weakening of elastic tissue leading to aneurysms underlies what disease?
Marfan syndrome
95
Mutations in TGF-β receptors causing defective synthesis of elastin and collagens I and III and potential aneurysms is associated with what disorder?
Loeys-Dietz Syndrome
96
Weak vascular walls due to **defective type III collagen** synthesis is a hallmark of the vascular forms of which syndrome?
Ehlers-Danlos Syndrome
97
There is a nutritional basis for aneurysm formation in people with which vitamin deficiency?
Vitamin C (scurvy)
98
Increased expression of what by macrophages in atherosclerotic plaques or in vasculitis may contribute to aneurysm formation?
MMP
99
The release of elastolytic MMP from macrophages is stimulated by what cytokines and is often seen in AAA's?
IL-4 and IL-10
100
Systemic HTN can cause **significant narrowing of arterioles of the vasa vasorum**, which causes ischemia of which part of the vessel?
**Outer medial** ischemia
101
**Loss of vascular wall elastic tissue**/ineffective elastic synthesis, with disrupted and disorganized elastin filaments and **increased ground substance (glycosaminoglycan)** gives what hallmark histological finding?
**Cystic medial degeneration**
102
What is a final common result of different conditions, including ischemic medial damage and **Marfan** syndrome?
Cystic medial degeneration
103
Which finding characteristic of late stage tertiary syphillis is a cause of aortic aneurysms?
Predilection for which vessels?
- Obliterative endarteritis
- Predilection for **small vessels**, including those of **vasa vasorum** of the **thoracic aorta**
104
The obliterative endarteritis of late-stage tertiary syphillis leads to what vascular/heart complications?
- **Ischemic injury** of the **aortic media** and **aneursymal dilation**
- Sometimes involving the **aortic valve annulus (aortic valve regurgitation**)
105
The 2 most important causes of aortic aneurysms are what?
Which is a greater factor in AAA's and which for ascending aortic aneurysms?
1. **Atherosclerosis** = AAA's
2. **HTN** = ascending aortic aneurysms
106
Mycotic aneurysms can originate via what 3 ways?
1. Embolization of a septic embolus (usually as complication of **infective endocarditis**)
2. **Extension** of an adjacent suppurative process
3. **Circulating organisms** directly infecting arterial walls
107
AAA's occur in the abdominal area most typically where?
**Below** the **renal arteries** and **above** bifurcation of the aorta
108
AAA's are characterized by severe atherosclerosis of the aorta, and are frequently covered by what?
Bland, laminated, poorly organized **mural thrombus**
109
AAA is often accompanied by smaller aneurysms in which arteries?
Iliac arteries
110
Which type of AAA is more common in younger patients and presentation includes back pain and elevated inflammatory markers?
Inflammatory AAA
111
Inflammatory AAA's are characterized by what type of inflammation and inflammatory infiltrate?
Abundant **lymphoplasmacytic** inflammation w/ **many macrophages** (and even **giant cells**)
112
Which variant of AAA is associated with aortitis and periaortitits that weakens the wall and may also have sx's associated with affected pancreas, bilirary system, and salivary glands?
IgG4-related disease
113
Why is recognition of IgG4-related disease as a variant cause of AAA important?
Responds **well** to steroid therapy
114
Which variant of AAA is due to lodging of circulating microorganisms in the wall w/ suppuration further destroying the media, potentiating rapid dilation and rupture?
Mycotic AAA
115
AAA's of which size are usually managed aggressively via surgery?
5cm or \>
116
What are 4 potential complications of an AAA?
- **Rupture** into peritoneal cavity or retroperitoneal tissues w/ hemorrhage
- **Obstruction** of vessel branching off of aorta (iliac, renal, mesenteric, or vertebral as.)
- **Embolism** from atheroma or mural thrombus
- **Impingement** on adjacent structure (i.e., compressed ureter or erosion of vertebra)
117
Thoracic aortic aneurysms are most commonly due to what?
May also be caused by what congenital defects?
- **Most common** = HTN
- Also seen in **Marfan** **syndrome** and **Loeys-Dietz syndrome**
118
What are some of the major signs/sx's of thoracic aortic aneurysms due to their location?
- **Impingement --\>** **Resp. difficulties** or **Dysphagia** or **Persistent cough** (recurrent laryngeal n.)
- **Pain** due to **erosion** of bone (ie **ribs** and **vertebral bodies**)
- **Aortic valve dilation** w/ **valve insufficiency** or narrowing
- **RUPTURE!**
119
Most patients with syphilitic aneurysms die of?
**Heart failure** 2' to **aortic valvular incompetence**
120
Aortic dissection occurs principally in what 2 groups of patients?
- **Men** aged **40-60 yo** w/ HTN
- **Younger adults** w/ disorders of CT affecting the aorta (i.e., **Marfan**)
121
Sudden onset of **severe** chest pain (usually beginning in anterior chest), **radiating back between the scapulae** and **moving downward** is the classic presentation of what?
Aortic Dissection
122
Aortic dissections can be catastrophic if what occurs?
Rupture through the **adventitia** --\> **massive** **hemorrhage** into adjacent spaces (i.e., thoracic or abdominal cavities) or **cardiac tamponade** (hemorrage into pericardial sac)
123
What is the major risk factor for aortic dissection?
HTN
124
Aortas of patients with HTN have **what type of hypertrophy** and degenerative changes associated with **loss of what**?
- **Medial** hypertrophy of the vasa vasorum
- Degenerative changes w/ loss of **medial smooth m. cells + disorganized ECM**
125
What is the most frequent pre-existing histologically detectable lesion in aortic dissections?
Inflammation?
**Cystic medial degeneration** and inflammation is **absent**
126
Most aortic dissections arise where?
Initiates via what type of tear?
**- Ascending aorta** within **10cm** of the **aortic valve**
**-** Via an **intimal tear**
127
If a dissecting hematoma from an aortic dissection re-enters the lumen of the aorta through a 2nd distal intimal tear, creates a new false vascular channel known as?
Over time these false channels can be endotheliazed to become recognizable as?
- "**Double-barreled aorta**"
- **Chronic dissections**
128
The more common (and dangerous) aortic dissections, type A dissections involve what?
- **B****oth**the**ascending**and**descending** aorta
- Or just the **ascending aorta**
129
Aortic dissections which extend into and involve the spinal arteries can cause what?
Transverse myelitis
130
Most common cause of death from aortic dissections is due to what?
Rupture into the **pericardial**, **pleural**, or **peritoneal cavities**
131
Retrograde dissection into the aortic root can lead to what?
Dilation of **aortic valve** --\> **aortic valve insufficiency**
132
How are type A dissections dealt with at clinical presentation?
- **INTENSIVE anti-hypertensive** therapy
- **Surgical** repair of **intimal tear**
133
How are type B dissections managed clinically?
**Conservatively**; with surgery or anti-hypertensive therapy
