04.07 - Atherosclerosis 1 and 2 (Nichols)

Question 1

5 major modifiable risk factors for atherosclerosis

Answer 1

Smoking, HTN, Obesity, DM, Dyslipidemia

Question 2

___ causes 20-25% of fatal acute MI’s

Answer 2

Superficial erosion of coronary atheromata

Question 3

2 most important causes of endothelial dysfunction

Answer 3

hemodynamic disturbances; Hypercholesterolemia

Question 4

3 Characteristics of Endothelial Dysfunction

Answer 4

Impaired endothelium-dependent vasodilation, Hypercoagulable states, increased oxygen free radical production

Question 5

3 Factors that maintain SM cells in quiescent state

Answer 5

Heparan, NO, TGF-alpha

Question 6

3 Major components of ECM in plaque

Answer 6

Collagen, Elastic Fibers, Proteoglycans

Question 7

95% of HTN is

Answer 7

Idiopathic (Essential HTN)

Question 8

Action of Lp-PLA2

Answer 8

Travels with circulating LDL and Hydrolyzes oxidized phospholipids in LDL

Question 9

Action of Products of Lp-PLA2 reaction generated in atherosclerotic lesions

Answer 9

Upregulate MCP-1, ICAM-1, and VCAM-1 on endothelial cells

Question 10

Actions of Myocardial Natriuretic Peptides

Answer 10

Inhibit Na resorption –> Diuresis; Also systemic Vasodilation

Question 11

Arteries v Veins: Which are more prone to penetration by tumors or inflammatory processes?

Answer 11

Veins

Question 12

Arteriosclerosis literally definition

Answer 12

Hardening of arteries

Question 13

Atheroscerlosis is characterized by

Answer 13

Presence of intimal lesions called Atheromas

Question 14

Canakinumab

Answer 14

IL-1beta mab

Question 15

Cause of Homozygous Familial Hypercholesterolemia

Answer 15

Defective LDL receptors and inadequate LDL uptake

Question 16

Cause of Hyaline Arteriolosclerosis

Answer 16

Leakage of plasma components across injured endothelial cells; Increased ECM production by SM cells in response to chronic stress

Question 17

Causes of Artery Amyloidosis (3)

Answer 17

Plasma Cell Dyscrasia; Chronic Systemic Inflammation (esp RA); Genetic (esp TTR)

Question 18

Causes of Fibrinoid Necrosis (2)

Answer 18

Malignant HTN; Autoimmune Vasculitis, esp. PAN

Question 19

Causes of Hyaline Arteriolosclerosis (2)

Answer 19

Benign HTN, DM

Question 20

Causes of Hyperplastic Arteriolosclerosis (2)

Answer 20

Malignant HTN; Autoimmune: Scleroderma, Lupus

Question 21

Cholesterol crystals contribute to development of atherosclerosis by activating

Answer 21

Inflammasome in Mac’s –> IL-1 production

Question 22

Color of young vs old fibrosis

Answer 22

Young is clear, Old is dark pink

Question 23

Complication of Fibromuscular Dysplasia in Renal Arteries

Answer 23

Renovascular HTN

Question 24

Complications of Fibromuscular Dysplasia

Answer 24

Luminal Stenosis, Abnormal Vessel Spasm that reduces vascular flow

Question 25

CRP levels strongly and independently predict risk of

Answer 25

MI, Stroke, PVD, SCD

Question 26

CRP secreted by cells within atherosclerotic plaque can

Answer 26

activate endothelial cells --> increase adhesiveness and pro-thrombotic state

Question 27

Cutoff for Malignant HTN

Answer 27

200/120

Question 28

Darapladib

Answer 28

Small molecule inhibitor of Lp-PLA2

Question 29

Determinants of Plaque Vulnerability

Answer 29

Thinness of Fibrous Cap; Size of Lipid Core; Amount of Inflammation, Amount of Calcification

Question 30

Dominant lipids in atheromatous plaques

Answer 30

Cholesterol and Cholesterol Esters

Question 31

Earliest atherosclerotic lesion is called

Answer 31

Fatty streak

Question 32

Early human atherosclerotic lesions begin at sites of

Answer 32

intact, but dysfunctional, endothelium

Question 33

Effect of Kinins and Prostaglandins on TPR

Answer 33

Both Decrease thru Vasodilation

Question 34

Effect of Lp-PLA2 bioactive lipid products on macrophages

Answer 34

Upregulated MCP-1 --> Secrete IL-1beta and undergo apoptosis

Question 35

Effect of MCP-1 on macrophages

Answer 35

Secrete IL-1b and Apoptosis

Question 36

Extensive AV fistulas can cause

Answer 36

high-output cardiac failure

Question 37

First 3 steps of Atherosclerosis

Answer 37

Malfunction of injured endothelial cells; Accumulation of lipid in intima; Leukocyte recruitment

Question 38

Focal irregular thickening of the walls of medium-sized and large muscular arteries due to combo of medial and intimal hyperplasia

Answer 38

What is Fibromuscular Dysplasia

Question 39

How does Ang II raise BP

Answer 39

(1) Vascular SM contraction; (2) stim aldosterone secretion; (3) Increase tubular Na resorption

Question 40

How does obesity contribute to atherosclerosis

Answer 40

Pro-inflammatory, Pro-thrombotic

Question 41

How does Thrombin initiate Inflammation

Answer 41

Cleaves PARs on leukocytes, endothelium, and other cells

Question 42

How is LDL modified in Tunica Intima

Answer 42

Oxidized and Glycated

Question 43

How is LDL taken up by macrophages

Answer 43

Not by LDL-R, but by a Scavenger Receptor

Question 44

Hyaline Arteriolosclerosis in kidney leads to

Answer 44

Nephrosclerosis (Glomerular Scarring)

Question 45

IL-1beta mab

Answer 45

Canakinumab

Question 46

In general, plaque inflammation increases

Answer 46

Collagen degradation and reduces collagen synthesis --> Destabilizing cap

Question 47

In malignant HTN, Hyperplastic Arteriolosclerosis changes are accompanied by

Answer 47

Fibrinoid Deposits and Vessel Wall Necrosis (necrotizing arteriolitis)

Question 48

Injured endothelial cells secrete

Answer 48

IL-1 and TNFalpha

Question 49

Injured endothelial cells secrete less

Answer 49

Superoxide Dismutase, NO, Prostacyclin

Question 50

Last step of Atherosclerosis

Answer 50

ECM (wavy collagen) deposition

Question 51

Major clinical consequences of Atherosclerosis

Answer 51

MI, Stroke, PVD, AA's

Question 52

Medial attenuation between focal segments of thickened wall prone to rupture

Answer 52

Fibromuscular Dysplasia

Question 53

Monckeberg Medial Sclerosis is characterized by

Answer 53

Calcific deposits in muscular arteries (>50, do not encroach on lumen)

Question 54

Morphology of Fatty Streaks

Answer 54

Yellow, flat, elongated, minimally raised

Question 55

Most important determinant of stroke volume

Answer 55

Filling Pressure (regulated by sodium homeostasis)

Question 56

Most important independent risk factor for atherosclerosis

Answer 56

Family History

Question 57

Mutations in ENaC lead to

Answer 57

Increased distal tubular resorption of Na induced by Aldosterone

Question 58

Neointimal vs Medial SM cells

Answer 58

Neointimal can't contract; Do have capacity to divide and have great synthetic capacity

Question 59

On its own, HTN can increase risk of IHD by __

Answer 59

60%

Question 60

Plaques in individuals taking statins have

Answer 60

more fibrous character (resistant to rupture)

Question 61

Problem with modified LDL being taken up by Scavenger Receptor

Answer 61

No feedback inhibition --> Take up too much

Question 62

Result of upregulation of MCP-1, ICAM-1, and VCAM-1 on endothelial cells

Answer 62

Vasodilate less in response to NO and undergo apoptosis

Question 63

Role of IFN gamma in plaques

Answer 63

Strongly inhibits SM cell production of collagen required to repair and maintain integrity of fibrous cap

Question 64

Ruptured plaques tend to have (3 things)

Answer 64

Thin Cap, Large Lipid Core, Abundant Inflammatory Cells

Question 65

Stereotypical response of vessel wall to any insult

Answer 65

Intimal thickening

Question 66

Superficial erosion causes what percent of fatal acute MI

Answer 66

20-25%

Question 67

T/F: Anti-Gout drugs can help atherosclerosis patients

Answer 67

True: Colchicine, 60% reduction of 3 year period

Question 68

T/F: Intimal thickening is always pathologic

Answer 68

False, part of normal aging

Question 69

T/F: Statins decrease the degree of stenosis as assessed on angiography

Answer 69

FALSE

Question 70

T/F: Statins result in significant reductions in atheroma volume

Answer 70

FALSE

Question 71

The pro-inflammatory role of Lp-PLA2 is mediated by

Answer 71

products of Lp-PLA2 reaction generated in athersclerotic lesions

Question 72

Thin-walled arterial outpouchings in cerebral vessels

Answer 72

Berry Aneurysms

Question 73

Top 3 most affected arteries with atherosclerosis

Answer 73

Infrareneal AA, Coronaries, Popliteals (Internal Carotids)

Question 74

Triggering the inflammasome results in activation of enzyme called

Answer 74

Caspace-1 --> Cleaves Pro-IL1b to IL-1b

Question 75

Two forms of small blood vessel disease that are HTN-related:

Answer 75

Hyaline Artiolosclerosis, Hyperplastic Arteriolosclerosis

Question 76

Type of HTN associated with Hyaline Arteriolosclerosis

Answer 76

Benign/Mild

Question 77

Up to ___ % of events due to atherosclerosis are from plaque rupture

Answer 77

75

Question 78

What activates inflammasome in mac's

Answer 78

Cholesterol Chrystals

Question 79

What boosts production of interstitial collagenases in macrophages?

Answer 79

CD 40 ligand on T cells

Question 80

What BP threshold is associated with increased risk of atherosclerosis

Answer 80

140/90

Question 81

What causes renin release besides low pressure

Answer 81

Circulating Catecholamines, Low Sodium in Distal Convoluted Tubules

Question 82

What does Aldosterone resorp and secrete

Answer 82

Resorb Na, Secrete K

Question 83

What else beside IL-1 do Mac's release

Answer 83

ROS --> LDL oxidation and growth factors that stimulate SM cell proliferation

Question 84

What is Fibromuscular Dysplasia

Answer 84

Focal irregular thickening of the walls of medium-sized and large muscular arteries due to combo of medial and intimal hyperplasia

Question 85

What is important about vasa vasorum formed in arteries that don't normally have

Answer 85

Prone to rupture

Question 86

What leads to conversion of Fatty Streak to Atheroma

Answer 86

Intimal SM cell proliferation and ECM deposition

Question 87

What mediates pro-inflammatory role of Lp-PLA2

Answer 87

Bioactive lipid products of Lp-PLA2 rxn generated in athersclerotic lesions

Question 88

What produces the MMPs implicating in degradating plaque collagen

Answer 88

Macrophages: MMP-1, MMP-8, MMP-13

Question 89

What regulates Filling Pressure

Answer 89

Sodium Homeostasis

Question 90

What T cell product is implicated in inhibiting the ability of SM cells to make new collage

Answer 90

Interferon Gamma

Question 91

What upregulates expression of MCP-1, ICAM-1, and VCAM-1 on endothelial cells

Answer 91

Bioactive lipid products of Lp-PLA2 rxn generated in athersclerotic lesions

Question 92

What women are protected against Atherosclerosis

Answer 92

Premenopausal

Question 93

When can Hyaline Arteriolosclerosis be seen in absence of HTN

Answer 93

Old People; Diabetic Microangiopathy

Question 94

When does Fibromuscular Dysplasia typically occur

Answer 94

Young women

Question 95

When is there low sodium levels in distal convoluted renal tubules

Answer 95

When GFR falls (when CO low) --> Increased Na resorption by proximal tubules, lower levels more distally

Question 96

Which come first in SHODDY

Answer 96

Smoking, then Obesity, then HTN

Question 97

Why is inhibiting collagen production by SM cells bad in plaque

Answer 97

Collagen needed to maintain integrity of fibrous cap

Question 98

With chronic hyperlipidemia, lipoproteins accumulate within intima, where they generate 2 pathogenic derivatives:

Answer 98

Oxidized LDL, Cholesterol Crystals

Question 99

Without appropriate tx, 50% of HTN pts die of

Answer 99

IHD or CHF (another 1/3 of stroke)