TOPIC TWO: HYPERTENSION AND ATHEROSCLEROSIS Flashcards
1
Q
What is tachycardia
A
High heart rate
2
Q
What is hypernatremia
A
high sodium in the blood
3
Q
What is normal sodium levels
A
125 - 135 mmol/L
4
Q
What is hypertension
A
High blood pressure
5
Q
What is the systolic and diastolic blood pressure indicative of hypertension
A
Systolic: ≥ 135mmHg
Diastolic: ≥ 85mmHg
6
Q
What were the old standards to diagnose hypertension
A
140/90
7
Q
What is diastolic pressure
A
Pressure exerted on the inside of the blood vessels by the blood when the heart is in relaxation
8
Q
What is systolic pressure
A
Pressure exerted on the inside of the blood vessels by the blood when the heart is in systole (contracting)
9
Q
What is the device used to diagnose HTN
A
Automated blood pressure cuff
10
Q
Do people always have symptoms of HTN
A
NO! It can be asymptomatic, but the damage is already done - silent killer
11
Q
What does primary/essential HNT mean and what % of HTN fall under this category
A
Unknown cause
90-95% of patients
12
Q
What does secondary HNT mean and what % of HTN fall under this category
A
High blood pressure caused by something else (disease, medication etc.)
5-10%
13
Q
How much of an increase in HTN has there been over time
A
60%
14
Q
Why has there been an increase in hypertension
A
More awareness - more people are being tested, more people are being diagnosed
More risk factors - diabetes, obesity, sedentary behaviour
Women are more likely to visit the doctor therefore more likely to be diagnosed
15
Q
What are some consequences of HTN (6)
A
Heart disease
- Left ventricular hypertrophy
- Coronary heart disease
- Heart failure
Kidney failure Peripheral Vascular Disease Retinopathy Hemorrhage and stroke - Could possibly lead to dementia Impotence (in men)
16
Q
Do people die from HTN?
A
NO
People die from what HTN causes
- MIs
- Heart failure
- Ischemic heart disease
17
Q
Anatomy of a Vessel
What are the three layers
A
Tunica intima/Interna
Tunica media
Tunica externa (adventitia)
18
Q
Anatomy of a Vessel
Where is the tunica intima located
What is it made of
A
The most internal part of the blood vessel, closest to the lumen
Made of endothelium and connective tissue that makes direct contact with the blood
19
Q
Anatomy of a Vessel
What is the lumen
A
Open space where the blood flows through
20
Q
Anatomy of a Vessel
What does the tunica intima release
A
Endothelins
21
Q
Anatomy of a Vessel
What are endothelins
A
Vasoactive substance
Vasoconstrictor that acts on the smooth muscle in the tunica media to cause vasoconstriction
22
Q
Anatomy of a Vessel
Where is the tunica media located
What is it composed of
A
The middle layer
Composed of smooth muscle and connective tissue
23
Q
Anatomy of a Vessel
Where is the tunica external located
What is it composed of
A
Outer layer
Sheath of connective tissue keeping the vessel in place
24
Q
What variables affect blood flow and pressure (5)
A
Compliance (most relevant) Cardiac output Volume of blood Viscosity Blood vessel length and diameter
25
How does compliance affect blood flow and pressure
What is the definition
Compliance is the ability to expand and the degree fo resistance, vascular tone (ability for the vessel to constrict and react)
We want a good vascular tone and a low degree of resistance so that the blood can flow easily and the heart does not have to work as hard to pump the blood
26
How does cardiac output affect blood flow and pressure
What is the definition
What receptors control it
What activates it
Cardiac output is the amount of blood pumped by the heart (L/min)
The beta receptors on the heart control the degree of contractility
The beta receptors are activate by the SNS
27
How does volume of blood affect blood flow and pressure
Greater the volume of blood, the greater the pressure
28
What is a diuretic
A water pill which deceases blood volume by decreasing H2O in the blood
29
How does viscosity affect blood flow and pressure
The more viscous, the greater the pressure exerted on the vessel wall
30
How does blood vessel length affect blood flow and pressure
The longer the vessel, the greater the resistance and the lower the flow
The farther away from the heart (longer the vessel) means higher resistance and lower flow
31
What is the relationship between resistance and pressure
When you increase resistance, you increase pressure
32
What is the relationship between vessel diameter and resistance
Resistance is inversely proportional to diameter
A slight decrease in diameter leads to a huge increase in resistance
33
What is the formula for resistance related to radius
Resistance = 1/radius^4
34
What is Atherosclerosis
Narrowing and hardening of the arteries due to plaque build up
Blood flow is significantly changed when there is narrowing of the vessel (increased resistance)
35
What is endothelial dysfunction
When the endothelium doesn't produce or respond to vascoactive substances
There is decreased vascular tone and responsiveness to vasoactive substances. Therefore the blood vessel cannot constrict and dilate in a healthy manner which can lead to hypertension over time
36
Where are the endothelial cells and what do they do
The endothelial cells line the intima
Normally produce or respond to vasoactive substances
37
What are vasoactive substances
Substances that act on the smooth muscle of the blood vessels to cause construction and dilation
38
What type of vasoactive substance is Nitric Oxide (NO)
Vasodilator
39
What type of vasoactive substance is endothelin
Vasoconstrictor
40
What type of vasoactive substance is prostacyclin
Vasodilator
41
How does endothelial dysfunction work
Stiff vessels (that are not responding/producing to vasoactive substances) lead to increased blood pressure and increases sheer stress which results in endothelial dysfunction
42
What is the results of endothelial dysfunction (NO)
There is a reduction in nitric oxide synthase which results in less NO production
NO is a vasodilator therefore there is more constriction
43
What is the result of endothelial dysfunction and ADMA
What does ADMA usually do
There is an increase in asymmetric dimethylarginine (ADMA)
ADMA blocks the production of NO from L-arginine
44
Is atherosclerosis a static or dynamic process
Dynamic
45
What are the other bodily processes involved in atherosclerosis
The immune system + inflammation
46
What is the mediator of atheromata formation (general)
Immune cells
There are many immunes cells involved and some are located in the atheromata as well
47
What is an atheromata and where is it located
Accumulation of debris under the intima layer of blood vessel
48
What is innate immunity
Immune response that happens quickly in the body without previous exposure or education
Happens right away
49
What is adaptive immunity
Immunes response that occurs after "education" or exposure to microbe
Slower
50
What are leukocytes
White blood cells
| Immune cells
51
What are the immune cells of interest here
Macrophages
Dendritic cell
Mast cell
52
Atherosclerosis formation
Step One
The LDL particle (previously traveling through the blood) slips between two endothelial cells which line the intima
53
Atherosclerosis formation
Step Two
The LDL particle becomes oxidized by 8-10 chemical reactions
54
Atherosclerosis formation
Step Three
The oxidized LDL particles are binding to the CD 36 scavenger receptor on the macrophage/monocyte
This is a spark of the reaction
55
Atherosclerosis formation
Step Four
Binding of the oxidized LDL causes a cascade of events
The monocyte/macrophages engulf the LDL - foam cell
There is a signal sent to the endothelial cells toe start expressing more adhesion cells to attract more monocytes to that particular spot
There is also an increase in adhesion of smooth muscle cells to macrophages and foam cells in plaque
There is movement of the smooth muscle cells from the media compartment to the intima compartment and they start to adhere to the immune cells
56
Atherosclerosis formation
Step Five
There is the development of foam cells when the macrophage engulfs the oxidized LDL particle
This is the key cell type found in atherosclerosis
57
Where is the atheroma forming
In the intima layer
58
What is in the atheroma
Smooth muscle cells have moved from the media to the intima
Macrophages, white blood cells and foam cells are here
The small intima compartment has now grown and is encroaching on the lumen
There is proliferation and movement of cells form the media to the intima
The blood vessel is remodelling in a detrimental way
59
Role of monocytes
When are they involved in atherosclerosis
Very early during lesion formation and later in the established lesion
60
Role of monocytes
What are they attached to and how
The endothelial cells via surface adhesion molecules
61
Role of monocytes
What doe they do
Cause inflammation, cause the production of cytokines and ROS, suppress NO and have an effect on TNF alpha and IL 1
Causes a cytokine storm
62
Role of monocytes
What do cytokines do
Direct monocytes to the intima, which continues as the lesion progresses
63
Role of monocytes
What do monocytes express that are essential for the SPARK of atherosclerosis
CD36 receptors
Oxidized LDL binds to CD36 receptors
64
Role of monocytes
What do TLR do and what cells express them
Monocytes and macrophages have toll like receptors (TLR) that trigger pro inflammatory cytokine cascade (TNF, IL-1 increase)
65
Role of monocytes
How do activated monocytes lead to more tissue damage
Produce Matrix metalloprotienases (MMP) and ROS
66
Role of monocytes
What do MMP do
Enzymes that break down cellular matrix molecules like collagen
This is bad.
If a plaque forms, we want to keep it in one spot. Breaking down the collagen will allow the plaque to break off and move around. This can cause other diseases like stroke heart attack etc.
WE WANT THE PLAQUE TO STAY IN PLACE ONCE IT FORMS
67
Role of monocytes
What can ROS do to further damage the vessel
ROS can cause cellular and molecular damage
68
What are the most important immune cells for developing atheromatas
Monocytes/macrophages
69
Role of Dentritic cells
Present antigens (HLA) to T cells
Promotes a greater immune response
Crosstalk between the innate and adaptive immune system
70
Role of Mast Cells
Release vasoactive histamine and leukotrienes which increase vascular permeability (more LDL can slip through)
Causes an increase in IL-6 which enhances inflammatory cascade
IL-6 levels are generally higher in individuals with vascular disease
71
Role of Platelets
Secrete pro inflammatory cytokines and myeloid related protein (MRP)
- leads to endothelial cell apoptosis and thrombosis (blood clotting)
Platelet aggregation via platelet derived growth factors (PDGF), transforming growth factor (TGF-beta)
- This can lead to increased blood viscosity
- This coupled with the decreasing radius of the blood vessel results in the perfect storm of CVD
72
Does cardiac output contribute to HTN
yes
73
What NS contributes to cardiac output and how
SNS contributes to cardiac output through activation of the beta receptor which causes contractions
More contraction leads to greater cardiac output which can lead to HTN because volume is related to pressure
74
How does the SNS relate to peripheral vascular resistance (PVR)
How to PVR related to atherosclerosis
How does it all related to endothelial dysfunction
SNS also acts on the peripheral vascular resistance (PVR) by increasing the amount of intracellular calcium that the smooth muscles have causing more contraction and increased resistance
- PVR is one of the main contributors to essential HTN
Atherosclerosis contributes to PVR
Endothelial dysfunction is a part of atherosclerosis which can feedback on PVR and increase resistance
75
What does RAAS stand for
Renin angiotensin aldosterone system
76
What type of system is RAAS
Endocrine
77
What is the RAAS system really important for controlling
Blood pressure
78
What is the RAAS system in HTN patients
Overactive or uncontrolled
79
In healthy individuals, when is renin released
When there is decreased Na in the blood (dehydration)
When there is a decrease in BP (maybe due to hemorrhage)
SNS activation (fight or flight)
80
What organ secretes the renin substrate
The liver
81
What organ secretes renin
The kidney
82
What does renin do
Causes the conversion of renin substrate to angiotensin I
83
What converts angiotensin I to angiotensin II
Angiotensin converting enzyme (ACE)
84
What does angiotensin II control
Blood pressure
85
How does angiotensin II regulate BP (3 ways)
Acts directly on the blood vessels to cause vasoconstriction
Acts on the adrenal cortex causing secretion of a hormone called aldosterone
Causes secretion of antidiuretic hormone from the pituitary gland
86
Why does angiotensin II help when you have low BP
When you have low BP, you want your blood vessels to constrict, you want to retain water, and you want to retain Na
87
What does anti-diuretic hormones do
Retain water
88
What does aldosterone do
Retains Na at the level of the kidney (water retain via osmosis)
89
In health individuals what happens when you have increased salt in your diet (wrt angiotensin II)
There is reduced angiotensin II to maintain BP
Regardless of sodium intake, the BP should stay relatively the same by reducing angiotensin II
90
In HTN individuals what happens when you have increased salt in your diet (wrt angiotensin II)
Angiotensin II levels do not decrease, and BP therefore increases
Graph shifted to the right
91
In treated HTN individuals what happens when you have increased salt in your diet (wrt angiotensin II)
In individuals treated for hypertension, the graph is shifted to the left
Individuals BP increases, but not to the level of someone with HTN and is not treated with medication
Angiotensin blocker works so that the body still has some control on BP but the regulation is not as tight as normal individuals
Graph shifted to the left
92
What is causing the higher levels of angiotensin II in HTN patients
It is not really known
93
HTN and angiotensin II
Related to ACE
There is increased ACE activity in HTN patients, which would give rise to more angiotensin II
94
What is Bradykinin
What breaks down bradykinin
Bradykinin is involved in vasodilation
ACE breaks down bradykinin which means more vasconstriction and higher BP
95
What is the ANS composed of
The sympathetic and parasympathetic NS
96
What part of the ANS is often involved when talking about BP
The sympathetic NS
97
What happens when there is SNS activation (wrt epi and norepi)
There is increased release of epi and norepinephrine from the adrenal glands
98
What does epi and norepinephrine cause
Cause the beta receptors on the cardiac tissues to be activated
99
What happens when beta receptors are activated
Increased contraction and cardiac output
Increased blood leaving the heart
100
What is cardiac output the product of
Heartbeat and stroke volume
101
What else is released in response to SNS activation
What does this cause
Renin release
Will lead to PVR likely by angiotensin II binding to receptors on vessels causing vasoconstriction
102
What happens when patients are treated with Beta blockers
Reduced BP
103
What is endothelin
What does it cause a __ sensitive rise in ___
What is it an activator of
A vasoconstrictor
Responsible for the salt sensitive rise in BP
Angiotensin II should decrease in response to more salt, however if the blood Na stay high for a long time, endothelin is probably playing a larger role than the reduction of angiotensin II
Activator of RAAS
104
What is bradykinin
What is it inactivated by
What does ACE inhibitors do
Vasodilator
Inactivated by ACE
Increase bradykinin by presventin ACE and increasing bradykinin release
105
What is Nitric Oxide
What is it made by (cells)
What does anti-hypertensive medications do to the vessel
Vasodilator
Made by endothelium
Anti-hypertensive medication restores impaired NO production, but not smooth muscle response (NO resistance, irreversible)
- There is some damage that can be reversed, but there is part of endothelial dysfunction that is not reversible
106
What is atrial natriuretic peptide (ANP)
What is it produced by and when
What does it do
Vasodilator
Produced by the atria when blood volume increases
Increases Na and water excretion
It is a natural diuretic
107
What is the pressure for diagnosis of pulmonary hypertension (PHTN)
Mean pulmonary artery pressure >25 mmHg
108
Recall
Where is the pulmonary artery
Leaving the right ventricle
The afterload (resistance) that is pushing against is higher
109
What heart failure results from PHTN
Heart failure on the right side
110
What is heart failure
When the heart cannot pump to the rest of the body
111
What is PHTN a complication of
Left heart disease (left ventricular hypertrophy, hearth failure)
Could be a biomarker of underlying CVD
Could have a role of estrogen
Could be a role of infection
112
Is there a higher PHTN in men or women
Women
113
Where is there increased pressure in PHTN
Does PHTN cause diastolic dysfunction and what it is
What related to the mitral valve occurs
Increased left atrial pressure
Diastolic dysfunction (inability for the heart to relax)
Mitral valve regurgitation (when there is increased left arterial pressure, there can be increase in left ventrical pressure and the blood can flow the wrong way)
114
Is PHTN progressive and fatal?
Yes
115
Flow of PHTN
First there is vasoconstriction in the pulmonary artery making it harder for the right side of the heat to work and can lead to right side heart failure which can lead to total heart failure
116
Molecular mediators of PHTN (5)
Decrease NO
Increased ADMA (blocks NO) - less vasodilation
Increase thromboxane (clotting factor) - might make the blood more viscous
Increased endothelin 1 - Vasoconstrictor
Activation of Ca channels on SMC - more Ca therefore more contraction and vast constriction
117
COVID
What does the COVID spike protein bind to
What does this cause
Interacts with the lunge ACE2
Increase in the presence of ACE which will lead to vasoconstriction by angiotensin II
118
What type of association is there between angiotensin II and COVID severity
Linear relationship
Also with the RAAS system
119
COVID can cause... (5)
Endothelial dysfunction
Inhibition of NO
Microvascular disease
Dysfunction of ACE and ACE pathway - there is more Ace than ACE receptors which can lead to PHTN
Associated with cytokine storm (inflammatory response) - can lead to endocardial ischemia (lack of blood flow to the endocardium) which can lead to PHTN and right ventricle heart failure
120
How much BP reduction is associated with _% risk reduction in major cardiac events
Reduce systolic BP by 5 mmHg reduce your risk of major cardiac event by about 50%
121
Diet and BP
DASH diet include a low intake of fat and Na, high intake of vegetables
(Dietary approaches to stop hypertension)
There was a decrease in about 5 mmHg in BP in those that adhered the best compared to those that only adhere a little to the diet (#1)
122
Exercise and BP
Decrease in BP associated with a single session
Decrease in BP associated with several sessions
Exercise is a great tool to use to prevent the risk of many different chronic diseases
There is even a benefit of exercising once!
A single session of aerobic exercise results in a reduction of systolic BP between 5-8mmHg for about 11 hours
There is a reduction from 5-15 mmHg following several sessions
People mostly want to reduce systolic BP
The greatest change results from aerobic exercise and following a Mediterranean diet
123
What does exercise to direct on BP (6)
Improves artery compliance due to NO production
Improved renal function and fluid balance
Down-regulates renin and angiotensin II (beneficial for people with HTN)
Reduces PVR (mby through NO production)
Increases tissue perfusion (circulation)
Longterm: decrease SNS activity (less epi and Norepi (which bind to Beta receptors causing increase HR and contractility)
124
Exercise and BP
How does artery compliance relate
Artery compliance: the ability of the vessel to contract and dilate in response to vasoactive substances
Here we are talking specifically vasodilation in response to NO production
We increase the production of NOS (NO synthase) when we exercise, leading to more NO production
125
Exercise and BP
Here does Renal function relate
Better regulated fluid balance. Therefore we do not have high BV leading to high BP - we are better able to regulate the fluid in out body
126
Exercise and CVD
Benefits (3)
Improved glucose sensitivity
Lower LDL
Decrease weight
127
What is the recommended exercise
150 minutes per week
