Tutorial 7 - VD, Ath. & case studies

Question 1

Main forms of CVD (cardiovascular disease) (2)

Answer 1

1. Ischemia

2. Hemorrhagic stroke

Question 2

Define aneurysm?

Answer 2

excessive localized swelling of an artery

Question 3

Main consequences of vascular disease? (3)

Answer 3

1. Chest pain
2. myocardial infarction
3. heart failure

Question 4

myocardial infarction AKA?

Answer 4

heart attack

Question 5

State the major, early symptom of cardiovascular dysfunction?

Answer 5

Snoring!

Question 6

Explain ‘OSA’?

Answer 6

Obstructive Sleep Apnea:

• occurs due to collapsed airway
• causes loud snoring, breathing ceases periodically
• linked to CVS disease

Question 7

t/f: if someone snores - but is yet to develop OSA, they are not at any greater risk of CVD.

Answer 7

false - the risk for CVS disease begins with snoring, before it develops into CVD

Question 8

define atherosclerosis?

Answer 8

build up of fat/ cholesterol/ etc. in arterial walls, occluding lumen

Question 9

What is the first sign of carotid artery disease?

Answer 9

Intima-media thickness

Question 10

State the main means of detection, and progress tracking of atherosclerotic disease?

Answer 10

Carotid intima-media thickness

Question 11

How do snorers compare to non-snorers, in carotid intima-media thickness?

Answer 11

snorers thicker

Question 12

How do patients with CVD risk factors (smoking, diabetes etc.) compare to patients without, in carotid intima-media thickness?

Answer 12

not statistically different

Question 13

State the SBP & DBP of:

a hypotensive person

Answer 13

SBP - < 90

DBP - < 60

Question 14

State the SBP & DBP of:

Normal person

Answer 14

SBP = 90-119
DBP = 60-79

Question 15

State the SBP & DBP of:

Prehypertension

Answer 15

SBP = 120-139
DBP = 80-89

Question 16

State the SBP & DBP of:

Stage 1 hypertension

Answer 16

SBP = 140-159
DBP = 90-99

Question 17

State the SBP & DBP of:

Stage 2 hypertension

Answer 17

SBP = 160-179
DBP = 100-109

Question 18

State the SBP & DBP of:

Hypertensive urgency

Answer 18

SBP = ≥180 
DBP =  ≥110

Question 19

State the SBP & DBP of:

Isolated systolic hypertension

Answer 19

SBP = ≥160
DBP = <90

Question 20

State the main effects of high blood pressure?

Answer 20

1. Damages wall of arteries - creating microscopic tears which turn into scar tissue
2. Damaged arteries accumulate material (scar tissue provides lodging place) - cholesterol, platelets, fats and plaque build up. As the plaque builds, arteries narrow and harden.
3. HBP speeds up hardening of arteries

Question 21

Oxygen extraction from blood in the coronaries:

a. ) Depends on NO secretion
b. ) is maximal and can be modified by endogenous material
c. ) is maximal and cannot be modified by endogenous material
d. ) is not maximal

Answer 21

c

Question 22

Stenosis of a coronary tract becomes symptomatic:

a. ) When is more than 70% of section area
b. )

Answer 22

a

Question 23

Myocardial oxygen extraction from blood at rest is:

a. ) is very low (20-30%)
b. ) quite low (40-50%)
c. ) near max (60-80%)
d. ) maximal (99-100%)

Answer 23

c

Question 24

Damage due of hypoxia in the myocardium:

a. ) Start always in middle layer
b. ) start often in endocardial layer
c. ) start always from epicardial layer
d. ) start always in endocardial layers

Answer 24

d

Question 25

Maximal blood perfusion is achieved in the heart wall: a. ) during systole b. ) during diastole c. ) toward end of systole d. ) toward end of diastole

Answer 25

d

Question 26

Stroke volume in heart failure is by definition: a. ) Increased b. ) Decreased c. ) Normal d. ) Decreased only in pulmonary circulation

Answer 26

b

Question 27

Impaired NO-mediated vasodilation occurs: a. ) Only in high blood pressure patients b. ) Only during heart attack c. ) Only in diabetic patients in peripheral arteries and later on in coronaries d. ) in several diseases such as arteriosclerosis, diabetes, and high blood pressure

Answer 27

d

Question 28

Distributing arteries: a. ) are the major target of arteriosclerosis b. ) have a minimal layer of SM cells c. ) have biggest layer of SM cells d. ) have a thin wall

Answer 28

???

Question 29

Sub-epicardial flow starts to decrease: a. ) below mean coronary pressure of 35% b. ) below mean coronary pressure of 45% c. ) below mean coronary pressure of 25% d. ) occurs across cardiac cycle irrespective MAP?

Answer 29

c

Question 30

Sub-epicardial flow starts to decrease: a. ) below mean coronary pressure of 35% b. ) below mean coronary pressure of 45% c. ) below mean coronary pressure of 25% d. ) occurs across cardiac cycle irrespective MAP?

Answer 30

c

Question 31

t/f: age causes hardening of arteries, irrespective of blood pressure

Answer 31

true (somewhat) - age does cause the hardening of arteries, but high blood pressure may accelerate this

Question 32

Damaged arteries cause accumulation of plaque, hardening and narrowing. a. ) What is the plaque composed of? b. ) What pathologies may this give rise to?

Answer 32

a. ) Cholesterol, fats, platelets etc. | b. ) Peripheral artery disease, coronary artery disease

Question 33

Mechanisms at play, following reduced exposure to CVD risk factors: a. ) Oxidative stress? b. ) NO availability? c. ) Inflammatory processes? d. ) Cyclic blood pressure?

Answer 33

a. ) Decreased; increased anti-oxidant defense b. ) Increased c. ) Decreased d. ) Increased

Question 34

Mechanisms at play, following reduced exposure to CVD risk factors: a. ) Shear stress? b. ) SNS activity? c. ) Vascular tone?

Answer 34

a. ) Increased b. ) Decreased c. ) Decreased

Question 35

Mechanisms at play, following increased exposure to CVD risk factors: a. ) Oxidative stress? b. ) NO availability? c. ) Inflammatory processes? d. ) Mean blood pressure?

Answer 35

a. ) Increased; more reactive O2 species b. ) Decreased c. ) Increased d. ) Increased

Question 36

Mechanisms at play, following increased exposure to CVD risk factors: a. ) Shear stress? b. ) SNS activity? c. ) Vascular tone?

Answer 36

a. ) Decreased b. ) Increased c. ) Increased

Question 37

Normal breaths per minute?

Answer 37

14-16 ish

Question 38

Arteries are a ____ reservoir.

Answer 38

pressure reservoirs - this is why when the heart pumps out its SV, the arteries expand (temporarily storing the pressure) before contracting; thus maintaining the pressure

Question 39

Why are arteries considered a pressure reservoir?

Answer 39

As arteries are able to expand and recoil, due to elastic fibers in arterial wall

Question 40

What is systolic pressure? | according to MAURO

Answer 40

MAXIMUM pressure occurring during systole

Question 41

What is diastolic pressure?

Answer 41

Pressure occurring during diastole (not necessarily maximum)

Question 42

Stage 1 hypertension - does it call for drug administer?

Answer 42

Yes

Question 43

Does prehypertension call for drug administer?

Answer 43

No - monitor it over time, adapt in lifestyle hopefully

Question 44

t/f: atherosclerosis is an inflammatory disease

Answer 44

true

Question 45

Atherosclerosis: a. ) Acute or chronic disease? b. ) Is it deadly? c. ) Occurs in veins or arteries? Of what size?

Answer 45

a. ) Chronic b. ) Yes c. ) Large arteries

Question 46

*Not a question* | Situation "John" is in assessment 3. Ensure to say that his BP must be monitored at least daily.

Answer 46

*Not a question* | Situation "John" is in assessment 3. Ensure to say that his BP must be monitored at least daily.

Question 47

Atherosclerosis: a. ) Is a primary cause of what? b. ) In westernized world, underlies _% of all deaths?

Answer 47

a. ) Heart disease, stroke | b. ) 50%

Question 48

CVD causes _% of all deaths in north america

Answer 48

35%

Question 49

Best way to reduce BP?

Answer 49

Exercise; lose weight

Question 50

State the 4 main physiological complications of atherosclerosis, as developed chronologically?

Answer 50

1. Endothelial dysfunction 2. Fatty streak formation 3. Advanced complicated lesion formation 4. Unstable fibrous plaque formation

Question 51

State main risk factors for developing hypertension?

Answer 51

1. Environmental - salt intake, tobacco, obesity, alcohol, 2. Genetic 3. Gene-environment Interaction - race, gender

Question 52

Explain how atherosclerosis begins (first main complication)?

Answer 52

Endothelial dysfunction: - increased permeability to lipoproteins/ other plasma constituents - migration of leukocytes into artery wall

Question 53

Endothelial dysfunction associated with atherosclerosis is partly characterized by increased permeability to lipoproteins and other plasma constituents. What mediates this?

Answer 53

- NO - prostacyclin - PDGF - ANG II - endothelin - up-regulation of leukocyte adhesion molecules (L-selectin, integrins, platelet-endothelial-cell-adhesion-molecule-1, vascular-cell-adhesion-molecule-1)

Question 54

Endothelial dysfunction associated with atherosclerosis is partly characterized by migration of leukocytes into artery wall. What mediates this?

Answer 54

- oxidized low-density lipoprotein - monocyte chemotactic protein 1 - IL-8 - PDGF - macrophage colony-stimulating factor - osteopontin

Question 55

The second stage of atherosclerosis is fatty-streak formation: a. ) What do the fatty streaks initially consist of? b. ) What are the fatty streaks later joined by?

Answer 55

a. ) Monocytes, macrophages and T lymphocytes (all lipid laden). b. ) smooth muscle cells

Question 56

The second stage of atherosclerosis is fatty-streak formation: What are the steps involved in this process?

Answer 56

1. Smooth muscle cell migration 2. T-cell activation 3. Foam cell formation 4. Platelet adherence and aggregation

Question 57

The second stage of atherosclerosis is fatty-streak formation: What stimulates the first step in this stage?

Answer 57

Smooth muscle cell migration - stimulated by: - PDGF - Fibroblast Growth Factor 2 - transforming growth factor b

Question 58

The second stage of atherosclerosis is fatty-streak formation: What mediates the second step in this stage?

Answer 58

T cell activation - mediated by: - tumor necrosis factor A - IL-2 - granulocyte-macrophage colony-stimulating factor

Question 59

The second stage of atherosclerosis is fatty-streak formation: What mediates the third step in this stage?

Answer 59

Foam cell formation - mediated by: - tumor necrosis factor A - IL-1 - macrophage colony-stimulating factor - oxidized low density lipoprotein

Question 60

The second stage of atherosclerosis is fatty-streak formation: What stimulates the fourth step in this stage?

Answer 60

Platelet adherence and aggregation - stimulated by: - integrins - P-selectin - fibrin - thromboxane A2 - tissue factor

Question 61

HDL are (protective/ unprotective), at (a certain range/ any amount).

Answer 61

HDL is protective; within a certain range

Question 62

Provide an explanation as to how the third stage of atherosclerosis takes place?

Answer 62

Formation of advanced, complicated lesions: 1. fatty streak forms fibrous cap walling off lesion from lumen (healing/ fibrous response to injury) 2. Leukocytes, lipid & debris contained within lesion may form necrotic core 3. Lesion expands as mediating factors enter and more leukocytes/ macrophages adhere

Question 63

The third stage of atherosclerosis is formation of advanced, complicated lesions: What factors stimulate macrophage accumulation?

Answer 63

- macrophage colony-stimulating factor - monocyte chemotactic proteins 1 - oxidized low density lipoprotein

Question 64

The necrotic core forming during atherosclerosis: a. ) Forms during which stage & step of the disease? b. ) Is the result of what?

Answer 64

a. ) Stage 3 (formation of advanced, complicated lesions). Step 2 of this stage (necrotic core formation). b. ) Necrotic core is result of apoptosis, necrosis, increased proteolytic activity & lipid accumulation

Question 65

The fibrous cap forming during atherosclerosis: a. ) Forms during which stage & step of the disease? b. ) Is the result of what?

Answer 65

a. ) Stage 3 (formation of advanced, complicated lesions). Step 1 of this stage (fibrous cap formation). b. ) Fibrous cap is result of: - increased activity in PDGF, transforming growth factor b, IL-1, tumor necrosis factor a, osteopontin - decreased CT degradation

Question 66

The fourth stage of atherosclerosis is unstable fibrous plaque formation: Describe the steps involved in this stage?

Answer 66

1. The rupture/ ulceration of the fibrous cap at areas where it is thinning 2. This leads to thrombus formation

Question 67

The fourth stage of atherosclerosis is unstable fibrous plaque formation: Why does the fibrous cap thin in this fourth stage, and what are other complications as a result?

Answer 67

1. Continued influx and activation of macrophages, leading to release of: - metalloprotinases - other proteolytic enzymes 2. These enzymes cause degradation of matrix 3. Degradation of matrix leads to hemorrhage from vasa vasorum/ lumen of artery 4. This can result in thrombus formation and occulsion of artery

Question 68

State triggers (risk factors) for atherosclerosis?

Answer 68

1. Hemodynamic forces and vortices (turbulent flow) 2. High blood pressure 3. Fat and cholesterol levels in blood 4. Genetic background (LDL, HDL, platelet reactivity) 5. Specific microbes (Chlamydia pneumoniae, CMV) 6. Microbiota in the gut (TMAO)

Question 69

How may the following factor(s) change to INCREASE risk of atherosclerosis: LDL/ HDL levels

Answer 69

LDL - increased | HDL - decreased

Question 70

How may the following factor(s) change to INCREASE risk of atherosclerosis: blood pressure

Answer 70

elevated

Question 71

How may the following factor(s) change to INCREASE risk of atherosclerosis: fat and cholesterol levels

Answer 71

increased

Question 72

How may the following factor(s) change to INCREASE risk of atherosclerosis: gender and age

Answer 72

male, risk increases at 45 for men and 60 for female

Question 73

t/f: most trigger mechanisms for atherosclerosis are self-maintained, and do not expand over time

Answer 73

false - trigger mechanisms for athersclerosis are self maintained but expand over time

Question 74

what is the largest 'characterizable factor' of athersclerosis - what's the biggest risk factor?

Answer 74

LDL levels (if high = bad bad)

Question 75

Effectors of atherosclerosis - what cells?

Answer 75

- smooth muscle cells - endothelial cells - macrophages - T cells (CD4, CD8, Th17) - platelets

Question 76

Effectors of atherosclerosis - what soluble mediators?

Answer 76

- NO - ANG II - IL-1, 8 - PDGF - CD40L, Gamma-interferon, osteopontin, MMP, MCP-1

Question 77

what is the 'critical point' in atherosclerosis mechanism?

Answer 77

fibrous capsule rupture

Question 78

platelet reactivity is a critical factor in the (beginning/ middle/ late) stage of athersclerosis

Answer 78

middle to late

Question 79

what causes the fibrous caps of lesions formed during atherosclerosis to become thin and vulnerable?

Answer 79

1. proteinases - collagenases, gelatinases, stromolysin | 2. inhibition of matrix secretion

Question 80

How may the following factor(s) change to INCREASE risk of atherosclerosis: infection. How does this occur?

Answer 80

Increased infection increases atherosclerosis. Infection causes: 1. systemic effects - induction of acute phase proteins 2. local effects - increased tissue factor expression, decreased plasminogen activator (PA)

Question 81

Actions of fibrinogen?

Answer 81

Increased... 1. endothelial permeability 2. monocyte transmigration 3. LDL accumulation 4. platelet reactivity 5. inflammation

Question 82

Define Pleiotropic?

Answer 82

producing multiple effects from a single gene

Question 83

What is the "biological modifier" of atherosclerosis?

Answer 83

Platelet activation - this is a plieotropic effector mechanism

Question 84

how do platelets and their activation effect atherosclerosis?

Answer 84

platelets release inflammatory and mitogenic substances into the microenvironment - altering proteolytic, chemotactic and ADHESIVE properties of endothelium

Question 85

t/f: platelet inhibition and/or modulation is a means of controlling atherosclerotic events in the late stages

Answer 85

true

Question 86

what are "foam cells", and how do they relate to atherosclerosis?

Answer 86

foam cells are macrophages which localize to fatty deposits on BV walls, they ingest LDL here and become laden with lipids giving them a foamy appearance they are an important step in fatty-streak formation

Question 87

what is TMAO?

Answer 87

Trimethylamine N-oxide: - gut microbiota-derived metabolite - microbiome produces it when eat choline (meat, egg, fish etc.) - makes resting platelets become hyper-reactive and enhances atherosclerosis (increases thrombus formation)

Question 88

arteriosclerosis vs atherosclerosis?

Answer 88

Both involve impeded BF in arteries - atherosclerosis is a type of arteriosclerosis, which occurs due to fatty deposit. arteriosclerosis - thickening, hardening and loss of elasticity in artery walls atherosclerosis - build up of fats/ cholesterol and other substances which can impede blood flow

Question 89

how may a diet high in red meat, poultry and other choline rich food affect atherosclerosis and why?

Answer 89

these foods contain choline which results in TMAO formation (microbiome), which increases platelet responsiveness and thrombus formation - increasing risk of atherosclerosis

Question 90

how are platelets effected by TMAO - why is it they become hyperreactive?

Answer 90

- increases thrombin, ADP, collagen levels | - stimulates release of intracellular Ca+2

Question 91

what do gut microorganisms turn choline into?

Answer 91

TMA, which is then converted to TMAO in the liver (trick question TMA)

Question 92

what main complication may arise from chronic atherosclerosis?

Answer 92

cardiovascular problems - myocardial infarction