Blood Vessels Flashcards
1
Q
Identify the blacked out portions of the artery shown
A
2
Q
What are the primary regulators of arterial blood pressure?
A
Arterioles (and small muscular arteries)
3
Q
What is the typical diameter of arterioles?
A
20-100 um
4
Q
What is the Hagen-Poiseuille equation?
A
5
Q
What are the categories of arteries?
A
- Large or elastic
- Medium-sized or muscular
- Small (less than or equal to 2 mm in diameter)
- vasa vasorum
6
Q
In veins, what is the site of leukocyte exudation and vascular leakage?
A
Postcapillary venules
7
Q
What is the approximate diameter of a capillary?
A
7-8 um or roughly the diameter of a red blood cell
8
Q
What size lymph vessels have valves?
A
larger lymph vessels
9
Q
Endothelial cells contain Weibel-Palade bodies. What the hell are these?
A
membrane-bound storage organelles that contain vWF
10
Q
What are the three types of capillaries?
A
Continuous
Fenestrated
Discontinuous
11
Q
What are three typical locations for continuous capillaries?
A
fat
muscle
nervous system
12
Q
What are three typical locations for fenestrated capillaries?
A
intestinal villi
endocrine glands
kidney glomeruli
13
Q
What are three typical locations for discontinuous capillaries?
A
liver
bone marrow
spleen
14
Q
Endothelial cells can elaborate anticoagulant, antithrombotic and fibrinolytic regulators. What are four of these?
A
Prostacyclin
Thrombomodulin
Heparin-like molecules
plasminogen activator
15
Q
Endothelium can elaborate prothrombotic molecules, what are three examples of these?
A
vWF
Tissue factor
Plasminogen activator inhibitor
16
Q
Endothelial cells have the ability to produce ECM, including collagen and proteoglycans. What are some examples of how they do this?
A
Modulation of blood flow and vascular reactivity
vasoconstrictors: endothelin, ACE
Vasodilators: NO and prostacyclin
17
Q
In what ways to endothelial cells contribute to regulation of inflammation and immunity?
A
IL-1
IL-6
chemokines
Adhesion molecules
- VCAM-1
ICAM
E-selectin
P-selectin
Histocompatibility antigens
18
Q
In what ways does endothelium regulate cell growth?
A
Growth stimulators: PDGF, CSF, FGF
Growth inhibitors: heparin, TGF-β
19
Q
Vascular smooth muscle is responsible for vasoconstriction and dilation. What are they regulated by?
A
- promoters
- Inhibitors
- RAAS
- Catecholamines
- Estrogen and osteopontin
20
Q
What does vascular smooth muscle do in response to injury?
A
Migrates to the intima and proliferates
21
Q
What does vascular smooth muscle synthesize post injury?
Elaborate?
A
Synthesizes
- collagen
- elastin
- proteoglycans
Elaborate
growth factors
cytokines
22
Q
What are the three vascular anomalies that we discussed? Which can rupture?
A
- Developmental (congenital, berry) aneurysms
- Arteriovenous Fistulas.
- Fibromuscular dysplasia
1 and 2 can rupture
23
Q
Focal irregular medial and intimal hyperplasia with thickening of walls of medium and large muscular arteries… would describe what?
A
Fibromuscular dysplasia
24
Q
Which component of blood pressure is more important in determining cardiovascular risk?
A
Systolic BP
25
What are five things htn is a risk factor for?
1. Aortic dissection
2. cerebral vascular accidents
3. hypertensive heart disease
4. coronary artery disease
5. renal failure
26
HTN is sustained chronically elevated pressure. What are the numbers we need to remember for Dr. Gomez?
140/90
27
BP is proportional to cardiac output and peripheral vascular resistance. What are some major facctors that determine blood pressure?
Age
Gender
BMI
Diet
Genetic variations in RAAS
Na+ retention
28
controlled hypertension with no short term problems describes what?
Benigh (essential HTN)
29
What are the guidlines for hypertensive urgency?
•systolic \>220 mm Hg or diastolic \>120 mm Hg with no evidence of target organ damage
30
What is described here?
•significant increase in B. P. associated with target organ damage (flame-shaped hemorrhages or exudates of fundus, renal failure, headache, angina, etc.)
Accelerated hypertension
31
What are the types of hypertensive emergencies we discussed?
Accelerated HTN
Malignant hypertension
32
Describe the process of renovascular hypertension
Renal artery stenosis
→↓glomerular flow +/- ↓pressure in the glomerulus afferent arteriole
→ ↑renin secretion
→ ↑angiotensin I
→ ↑angiotensin II
→1) vasoconstriction
→↑ peripheral resistance
→ 2) ↑ aldosterone
→↑ sodium reabsorption
→↑ blood volume
33
What is Liddle syndrome?
Liddle Syndrome – moderately severe salt sensitive hypertension due to Increased distal tubular reabsorption of Na+ with aldosterone stimulation
34
What disease process is shown here?
Where does this typically occur?
Atherosclerosis
primarily in elastic arteries and muscular arteries
35
What is this?
Where does it occur?
Arteriosclerosis
small arteries and arterioles
36
What is shown here?
Where does it typically occur?
In what populations?
Monckeberg Medial Calcific Sclerosis
Muscular arteries of those over 50 y/o, with no vessel lumen narrowing (can ossify)
37
What is shown here?
Who is this seen in?
1.Hyaline arteriolosclerosis - Protein deposition (hyalinized)
Seen in
* aging
* diabetes mellitus
* benign nephrosclerosis (hypertension)
38
What is shown here? When is this seen?
Hyperplastic arterioloslerosis,, cell death (onion skinning) with or without arteriolitis
Seen in malignant HTN
39
How does licorice cause HTN?
It contains aldosterone analogues. Someone who regularly eats licorice will have elevated Na+ concentrations and thus HTN.
40
What are some endocrine causes of 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
41
What are some renal causes of HTN?
Acute glomerulonephritis
Chronic renal disease
Polycystic disease
Renal artery stenosis
Renal vasculitis
Renin-producing tumors
42
What are the cardiovascular causes of HTN?
Coarctation of aorta
Polyarteritis nodosa
Increased intravascular volume
Increased cardiac output
Rigidity of the aorta
43
What are some neurologic causes of HTN?
Psychogenic
Increased intracranial pressure
Sleep apnea
Acute stress, including surgery
44
How do oral contraceptives contribute to HTN?
Increased Angiotensinogen
45
How does a 11B-hydrozylase deficiency contribute to HTN?
Increased aldosterone production, similar to effects from an aldosteronoma
46
What areas are prone to atherosclerosis?
Those with turbulent flow and low shear stress
47
Laminar flow induces endothelial genes for products that protect againts?
atherosclerosis (superoxide dismutase)
48
1. What characterizes Type I atherosclerosis?
2. What is its sequence in the atherosclerotic progression?
3. What is the main growth mechanism?
4. When is the onset?
5. What is the clinical correlation?
1. Isolated macrophage foam cells - "fatty dots"
2. First in the sequence, progresses to Type II
3. Mainly lipid accumulation
4. From first decade
5. Clinically silent
49
What characterizes Type II atherosclerosis?
What is its sequence in the atherosclerotic progression?
What is the main growth mechanism?
When is the onset?
What is the clinical correlation?
1. Mainly intracellular lipid accumulation - "fatty streak" lesions
2. Step II, progresses to step III
3. Lipid accumulation
4. First decade
5. Silent clinically
50
What characterizes Type III atherosclerosis?
What is its sequence in the atherosclerotic progression?
What is the main growth mechanism?
When is the onset?
What is the clinical correlation?
1. Type II changes and core small extracellular lipid pools.
2. Third, progressed to fourth
3. Third decade
4. Silent
51
What characterizes Type IV atherosclerosis?
What is its sequence in the atherosclerotic progression?
What is the main growth mechanism?
When is the onset?
What is the clinical correlation?
1. Type II changes and a core of extracellular lipid
2. Step 4, progresses to step five OR six
3. lipid accumulation
4. third decade
5. silent OR overt
52
What characterizes Type V atherosclerosis?
What is its sequence in the atherosclerotic progression?
What is the main growth mechanism?
When is the onset?
What is the clinical correlation?
1. Fibroatheroma - lipid core and fibrotic layer, or multiple lipid cores and fibrotic layers, or mainy calcific or mainly fibrotic
2. step five, progresses to step 6
3. Accelerated smooth muscle and collagen increase
4. Fourth decade
5. silent or overt
53
What characterizes Type VI atherosclerosis?
What is its sequence in the atherosclerotic progression?
What is the main growth mechanism?
When is the onset?
What is the clinical correlation?
1. complicated lesion - surfacce defect, hematoma-hemorrhage, thrombus
2. step6, final step
3. fourth decade
4. silent or overt
54
What stage of atherosclerosis is shown in this sample from the aorta of a 45 y/o male recently deceased from a CVA?
Stage IV, with diffuse and complicated lesions including an ulcerated plaque (open arrow) and a lesion with an overlying thrombus (closed arrow)
55
What is shown here?
Stage II atherosclerosis
Note the fatty streaks indicated by arrows on gross image and the presence of Fatty dot, macrophage derived foam cells.
56
Is this an example of complicated lesions?
No, this is mild atherosclerosis only, with fibrous plaques
57
Identify!
This is a coronary artery with atheromatous plaque
A - masson's trichrome stain
B- elastin stain
C- hematoxylin and eosin stain (revealing calcification and neovascularization)
58
Identify the indicated portions of the atherosclerotic plaque
1. Fibrous cap
2. necrotic center
3. media
59
Which example of these two vessels is more likely to rupture?
The one on the left, due to the narrow fibrous cap.
60
Is this plaque likely to rupture?
Why?
Yes, due to the invaginated and thin fibrous cap.
61
What is shown here?
A ruptured atherosclerotic plaque with a superimposed thrombus
62
What are the non-modifiable (constitutional) risk factors for atherosclerosis?
Genetic Abnormalities - familial hypercholesterolemia
Family history
Increasing age
Male gender
63
What are some modifiable risk factors for atherosclerosis?
Hyperlipidemia
HTN
Smoking
DM I or II
Inflammation
64
If you have two risk factors, how much does this increase your risk for atherosclerosis?
3 risk factors?
2 risk factors - 4 times the risk
3 risk factors - 7 times the risk
65
What constitutes metabolic syndrome?
Obesity
Dyslipidemia
hypertension
Insulin resistance
(may also see hypercoagulation and inflammatory state)
66
What is an example of a drug that inhibits HMG-CoA reductase?
Statins
67
Characterize cholesterol metabolism!
2/3 via LDL receptor pathway
1/3 via scavenger receptor pathway (oxidized LDL)
68
Where are most LDL receptors located?
~75% on hepatocytes
69
What does the LDL receptor bind?
What is the process that this event leads to?
Apolipoproteins B-100 and E on LDL and IDL.
1. →Endocytotic internalization
2. →↑Cytoplasmic cholesterol
3. → Inhibition of cholesterol synthesis
70
In what ways does LDL receptor binding inhibit cholesterol synthesis? (3)
1. Inhibition of 3-hydroxy-3-methylglutaryl (3-HMG) coenzyme A reductase, which is the rate limiting step in the synthetic pathway.
2. activates acyl-CoA: cholesterol acyltransferase (ACAT), which favors esterification and storage of excess cholesterol.
3. Down regulates the synthesis of cell surface LDL receptors
71
In addition to the inhibition of HMG-CoA reductase, what other effect do statins have on cholesterol metabolism?
They promote synthesis of LDL receptors
* ↓intracellular cholesterol allows ↑LDL receptor formation
72
What is the number for LDL that is where a patient is in need of therapy?
LDL-C \> or equal to 190 mg/dL
73
↑LDL, ↓ HDL and ↑Lp(a) are associated with ?
Increased atherosclerosis
74
What impact do estrogens have on lipid levels?
•↑ HDL &↓ LDL
75
What impact does estrogen replacement therapy have on the risk of heart attacks in post menopausal women?
None
76
What is the risk increase for coronary artery disease with oral contraceptives in women over 35 who also smoke?
2x Increased risk of coronary artery disease
77
What is mutated in familial hypercholesterolemia?
LDL receptor gene is mutated, leading to elevated LDL and IDL cholesterol in plasma.
78
What pathway for lipid elimination takes over in familial hypercholesterolemia?
Oxidized LDL receptors take over - the scavenger pathway
79
What is the most common class of familial hypercholesterolemia?
Type II - **Transport** to the golgi complex from the endoplasmic reticulum is impaired d/t abnormal protein folding.
80
What is the inheritance pattern of familial hypercholesterolemia?
Autosomal dominant
81
What are the three things shown in these images of a patient with familial hypercholesterolemia?
Is this patient hetero or homozygous?
1. Planar xanthoma
2. xanthelesma
3. Arcus Juvenilis (senilis in adult)
Homozygous
82
To what degree are heterozygous patients with familial hypercholesterolemias plasma cholesterol levels elevated?
2-3x
83
How much higher are plasma cholesterol levels in a patient who is a homozygote for the familial hypercholeterolemia mutation?
5x normal
84
What are the complications that arise d/t familial hypercholesterolemia?
1. Severe atherosclerosis
2. mitral valve stenosis
3. corneal arcus
4. Xanthomas
85
What are four other risk factors for atherosclerosis that we covered?
1. Elevated homocysteine
2. presence of lipoprotein a
3. Elevated plasminogen activator inhibitor 1
4. infections from **Chlamydia pneumoniae,** herpes virus and CMV
86
What is C-reactive protein? Where is it produced?
•Acute-phase reactant synthesized primarily by the liver
87
What are the roles of C-reactive protein?
* Has roles in opsonizing bacteria and activating complement
* Involved in endothelial adhesion of WBCs and thrombosis
88
What does C-reactive protein strongly and **independently** predict the risk for?
(4 things)
1. MI
2. Stroke
3. peripheral artery disease
4. sudden cardiac death
89
Does lowering CRP reduce cardiovascular risk?
No evidence of this... although smoking cessation, weight loss, statins and exercise lower C reactive protein and decrease risk.
