1
Q
Where is…
- fastest flow
- slowest flow
A
- so fastest flow will be in larger vessels (arteries and veins)
- capillary system: lot of cross sectional area, because it is the location of exchange and you would not get proper exchange if the flow was too fast
2
Q
What alters resistance?
A
- Diameter
- Viscosity
- Length
3
Q
Laminar flow
A
- smooth flow
4
Q
Turbulent flow
A
- disrupted flow
5
Q
Which part of vessel regulates blood flow to organs?
- What is unique about them?
A
- Arterioles
- They can contract and dilate; Have smooth muscle; Have endothelial cells
6
Q
Veins
- What is unique about them
- What happens when you increase venous tone?
A
- Can contract and dilate but not as good as arteries; Have some smooth muscle; Have endothelial cells
- They are less compliant, Can help to increase venous return
7
Q
what happens to blood flow at rest vs strenuous activity in skeletal muscle?
- What is skeletal muscle creating? what does it do?
- impact of sympathetic tone
- What happens to blood flow to skeletal muscles when you stop exercising? Why?
A
- Active hyperemia: demand for blood flow and oxygen from myocytes during exercise which results in body increasing blood flow to them
- CO2, lactic acid –> act as vasodilators
- still have a sympathetic tone there but the local factors have over-ridden it
- It decreases to go back to normal; Not producing as many metabolites and the metabolites currently there begin to wash out so you loose local response and blood flow decreases and size of vessel decreases and goes back to normal
8
Q
How do vasodilators work??
A
- Nitric oxide in endothelial cells relaxes out the smooth muscle
- In smooth muscle NO is going to activate cyclic GMP which is going to activate myosin light chain phosphatase/ deactivate myosin light chain kinase and you get dilation
9
Q
- what happens to blood flow at rest vs strenuous activity in Kidney and abdominal organs? what impacts it?
- How does it happen?
- What happens at cellular level?
- What causes contraction in smooth muscles versus skeletal/cardiac muscle?
A
- With sympathetic innervation you would decrease the flow to those because it is not as necessary for them to function at the moment
- Arterials are signaled to constrict through alpha adrenergic receptors
- Remember we are in smooth muscle.
- Calmodulin sequesters calcium and will bind to myosin light chain kinase and that activates the cross bridge formation
10
Q
what happens to blood flow at rest vs strenuous activity in Brain
- difference in blood flow?
- What phenomenon prevents increase blood flow to brain?
- how does it work?
- Why would you want to mediate blood flow to brain?
A
- There may be subtle changes between rest and exercise but overall there aren’t big changes
- Autoregulation– myogenic tone: way organs can mediate blood flow by reacting to metabolic demand
- So you increase blood flow -> vessel starts to dilate -> increase Ca stretch receptors -> increase in Ca in -> contraction occurs -> smaller diameter in vessel
- The brain is in a skull and if you increase flow too much it will increase pressure which can causes problems.
11
Q
What is role of endothelial cells?
A
- they release Nitric Oxide (specifically when responding to shear stress) -> leaks into smooth muscle and dilates the vessel
12
Q
What is vascular reactivity?
- What happens if the blood vessel no longer has this?
A
- Blood vessel responding to a stimulus or stress
- Will return to basal phase or depending upon whatever else is going on may just stay in basal state -> so it will not respond to stressful situation
13
Q
What is endothelial dysfunction and how does that relate to vascular reactivity?
A
- Endothelial cells are not responding to shear stress -> they don’t make NO -> do not have vascular reactivity (No cross reactivity between endothelial cells and smooth muscle)
- So if you have an increase in demand and need to dilate the vessel the endothelial vessels could no longer make NO and so you no longer have that dilation in response to that increase in cardiac demand
14
Q
What does S4 mean?
- What can cause this?
- What kind of remodeling do you think might be going on in his heart?
- Do you think he has some dysfunction?
- Do you think he has heart failure? why?
A
- normally means ventricular resistance, stiffening
- HTN, an increase in afterload
- Concentric, as in an afterload induced not a hypertrophic cardiomyopathy
- Possibly
- No, BP and pulse are high.The heart is functioning fine its just having to work against a really hard load right now so acutely the heart is good, but if it continuous to work against this type of force its going to possibly move on to failure and there is No JVD, trace edema even with the increased BP
15
Q
How do you explain his symptoms of chest pain on exertion in patient with high blood pressure and arteriosclerosis?
A
- Increased metabolism, increased O2 demand, decreased supply because he has blockage of his coronary artery; On top of that, the increased HR means that they have a shorter diastole –> further decreasing perfusion to the subendocardial tissue
16
Q
what mediates perfusion in the heart itself?
- how?
- normal when exercising?
- what happens with 40 yr old with some blockage? why?
- what determines that blood flow when there is atherosclerosis?
- what happens at 70%
A
- arterioles of coronary artery
- able to change their shape (can dilate and constrict)
- They dilate - So they increase the radius to help increase blood flow
- The arterioles still dilate to help mediate metabolic supply and demand but It’s not as efficient because they’re not able to receive as much blood as before because of the blockages
- degree of blockage
- vessels will dilate as much as they possibly can, but you’re not going to meet metabolic supply and demand
17
Q
What happens to vascular reactivity in arterioles with a patient who was a smoker with a sedentary lifestyle, and high fat diet?
- what would happen to endothelial layer?
A
- It would decrease
- You would have changes that can cause dysfunction - now those vessels will not respond as freely
18
Q
How does a patient get a thickened intima?
- difference between normal cells and fill in?
- What are the effects of this over time? Why?
- potential causes of this?
- pathway?
- what can this do to the heart?
A
- Smooth muscle cells that go in and fill in
- capable of proliferation, have contractile properties, motile, produce Collagen & they can respond to TGF beta
- Decreased elasticity because there’s thickening of the intima, Vessel reactivity decreases, Cant vasoconstrict as efficiently as it would bc you’ve lost some of that reactive smooth muscle that would normally respond, Collagen is deposited causing fibrosis and further decreasing contractile ability.
- HTN, Can have chronic sheer force; Smoking, can increase the endothelial damage by ROS and so that insult and damage can result in intimal thickening as seen on pt on the right; Poor diet, lack of exercise, Diabetes
which can cause damage to the vessels as well as cause sclerosis, arteriolosclerosis, etc - You have damage –> influx of some sort of fibroblast like cells (either fibroblast or smooth muscle cells) and they lay down collagen, thickening it –> vessels lose their vascular reactivity.
- Could decrease venous return, but now lets think about it in the arteriole side, it increases afterload
19
Q
Aneurysm
- How does it present histologically?
- Relate to Marfans
- Relate to Ehlers-Danlos Syndrome
- Atherosclerosis and Hypertension
A
- fairly concentric thickening of intima with outpouching
- The defect is in the fibrillin protein –> affecting the elastin in the media –> this will cause weakening of the elastic tissue, which can cause more dilation of the aorta –> aneurysm
- There’s abnormal synthesis of collagen; Kind of similar to Marfan’s - where you have weakening of the media because of abnormal collagen synthesis
- Most common problem
20
Q
How does atherosclerosis and hypertension cause an aneurysm?
- inhibitors of MMP
- biggest problem with aneurysm?
- Two most common places that they occur:
A
- causes intima thickening because there’s macrophages in the atherosclerotic plaques and that can lead to an increase in matrix metalloproteinases, and those can degrade the ECM and increase collagen deposition which will make the intima thickened and the media weakened.
- TMPs
- They can rupture, which is a medical emergency
- Abdominal aorta (Infrarenal above the bifurcation) and Circle of Willis
21
Q
Define
- true aneurysm (saccular)
- true aneurysm (fusiform)
- false aneurysm
- dissection
A
- bulges or balloons out on one side of the blood vessel.
- bulges or balloons out on all sides of the blood vessel; more common
- tear can occur on the inside layer of the vessel. As a result, blood fills in between the layers of the blood vessel wall creating a pseudoaneurysm.
- aneurysm that occurs with a tear in the artery wall that separates the 3 layers of the wall, rather than ballooning out the entire wall.
22
Q
why des HR increase with exercise?
- what happens to BP?
- hormone involved? what does it do?
A
- Sympathetics
- Increase in HR, increases CO which could lead to increase in pressure.
- Adrenaline/Epi; ou have epinephrine hitting most vascular beds that have alpha receptors mediating vasoconstriction but there are special beta 2 receptors on the blood vessels within skeletal muscle and when epinephrine binds to them they produce vasodilation.
23
Q
functional consequences of alpha constriction most place and beta dilation within the skeletal muscle
A
- Dilation to skeletal muscle because they need the extra oxygen and are making more waste (beta dilation)
- Constrict vessels to organs not being needed (alpha constriction)
24
Q
What is first step for dilation in skeletal muscles when exercising? second?
- how do we know this
A
- sympathetics, with nor-epi binding to beta receptors
- buildup of local metabolites
- people will increase their HR and ventilation slightly before they even start exercise, in anticipation of the exercise
25
What effect might the beta blocker have on their ability to exercise?
- could the effect on BP just be delayed?
- block that ability of the skeletal muscles to dilate in response to epinephrine, you're not going to get that big vasodilation, you can see an increase in BP and decrease in perfusion to the skeletal muscle.
- Yes, after a period of time when you exercise and buildup local metabolites, then that can cause the vasodilation to try and offset the increase in BP.
26
Beta 1 vs Beta 2 antagonist drugs
- beta 1 antagonists: to prevent the ability of the heart to increase its workload.
- there is not any Beta 1 antagonist drugs on market
- beta 2 agonists all the time- albuterol for asthma.
27
Difference of local metabolites build up in static vs dynamic exercise
- dynamic: you're contracting and relaxing so you do have periods when you get fresh blood into the muscle to wash away the metabolites
- static isometric contraction: it’s the same so you're reducing blood flow for the duration of the contraction. So you can have buildup of local metabolites occur more quickly with static isometric contraction as you might see with dynamic rhythmic exercise.
28
most rapid compensatory mechanism for high BP?
- how does it work?
- what does it do?
- can it go the other way?
- neural reflex and the arteriole baroreceptor reflex.
- You've got baroreceptors located in the loop of the kidney, aortic arch, carotids which are activated during stretch
- When responding to increase in pressure HR would decrease and sympathetic nerve activity decreases.
- yes it can correct low BP by increasing heart rate and then sympathetics would kick in a bit later
29
chronic compensatory mechanism for increased BP?
- describe the pathway
- any other ways for renin to be activated?
- renin angiotensin aldosterone pathway
- dehydration had a drop in total volume so the kidneys are going to be perfused less which causes increased renin from the juxtaglomerular cells-> increased renin is going to converge free floating angiotensinogen into angiotensin I which goes to the lungs to be converted by endogenous angiotensin converting enzymes into angiotensin II -> angiotensin binds A21 receptors on adrenal gland-> they synthesize and release aldosterone -> acts on the mineralocorticoid receptors -> produces epi
- Sympathetics
30
what does increase in sympathetics do to the heart?
sympathetics act on beta 1 receptors within the heart to increase HR by acting on the SA node, increasing automaticity. You also increase contractility. So increase CO, SV and HR.
31
what does increase in sympathetics do to the arterioles
the alpha receptors within the periphery constrict with sympathetic tone (smooth muscle constrics to increase total peripheral resistance) which tries to increase venous return, preload and potentially maintain compensated BP.
32
what does increase in sympathetics do to the venules
there are also alpha receptors in the vein to increase venous return, preload and potentially maintain compensated BP.
33
vasopressin system significance
| - inhibition
- can contribute to the responses to hypovolemia and dehydration.
- arterial baroreceptors.
34
Reflex to increase drinking
- angiotensin increase binds to AT1 (angiotensin) receptors in the hypothalamus to initiate some pronounced drinking behaviors
35
how would you determine whetherpatients blood pressure is the result of pain Or is he genuinely hypertensive?
get 24 hour ambulatory blood pressure monitoring
36
Effects of high BP chronically?
↑ left ventricular afterload because the heart has to work harder to eject blood through the aorta (this is because the aortic valve won’t open until the pressure generated in the LV is higher than the elevated BP in the aorta)àincreased left ventricular wall thickness (concentric hypertrophy) à diastolic dysfunction à Left atrium begins to dilateàL ventricle dilates (eccentric hypertrophy)àcontractile dysfunction/ systolic dysfunction (heart not able to pump as well as it should)
37
Why would patient stop taking BP meds?
- the ACE inhibitors can predispose people to a dry hacking cough, particularly women
- Propranolol can cause ED in men
38
What neural and humoral systems are involved in determining the patients blood pressure when it is chronic
- Baroreceptor reflex because Damaged heart --> reduced CO-->Low BP
- Arterial chemoreceptors because decrease in CO could starve the tissue for oxygen -> increase AP discharge during periods of hypoxia
39
What happens to neural response during increase in pressure (HTN)?
there are changes that occur within the receptors themselves, there are changes that occur within the central nervous system structures that integrate the baroreceptor afferent input. And they all cause this relationship to shift to a new operating point that's in a midpoint of the relationship.
40
What happens to neural response during decrease in pressure?
- the reflex can reset leftward because with time the reflexes reset, and you find yourself at this new operating point
41
What determines the normal level of blood pressure
- Renal mechanism by regulating blood volume and other factors that can control sympathetic outflow independently of the baroreceptor reflex.
- baroreceptor reflex is a buffering mechanism to try and stabilize arterial pressure.
42
Implantable treatment for HTN
implantable devices that are placed on the carotid sinus nerve that provide stimuli to the baroreceptor afferent fibers on an intermittent basis to cause sympatho inhibition to lower BP.
43
Would atherosclerosis of the carotid sinus have any effect on overall BP regulation?
anything that compromises the ability of that blood vessel to stretch can reduce the function of the baroreceptors.
44
How does obstructive sleep apnea (OSA) occur?
- what kicks in?
- reflexes as important contributor to
- what happens chronically?
- treatment
- when you're sleeping, gravitational forces cause the tongue to relapse and actually physically obstruct or block the upper airway.
- Episodes can last up to 10s and then there are changes in blood gases that eventually cause subconscious level of arousal, and you clear the tongue and you start breathing again. And this repeats over and over again.
- Chemoreceptors-They're activated during periods of hypoxia, hypercapnia -> afferent fibers transmit that information to the central nervous system, and evoke changes in vagal and sympathetic output
- there are adaptations that occur in the central nervous system that enables sympathetic nerve activity to remain elevated, even in the absence of a hypoxic stimulus.
- CPAP: continuous positive airway pressure; blows the low level of air down the nostrils.
45
Importance of evolving reflexes?
- baro reflexes
- chemp reflexes
- acute
- chronic
- protect you against falls or increases in blood pressure
- protect you against hypoxia, by stimulating ventilation, turn on sympathetics and divert blood to the heart and the brain, the most essential organs.
- in the acute phase they're protecting the body but these reflexes were not meant to be turned on chronically because of repetitive activation of these reflexes that become a source of a lot of the pathology.
- chronic term: you're actually trying to undo what these reflexes are doing.
46
What happens during cardiac heart failure?
- cardiac output
- SNS
- RAAS
- Cardiac output is decreased so try to compensate through
- sympathetics by increasing HR with nodes, increaing contractility through myocytes in ventricles, increase the constricting of veins and arteries which increases venour return which increases preload which increases afterload?
- RAAS will do same things as sympathetics to the vessels and then will have collecting ducts of kidneys increase Na and H2O reabsorption which increases the circulating volume and that increases pre-load which will increase after load
47
what happens pathophysiologically to heart during MI?
One of the coronary arteries has atherosclerosis and probably a very unstable, inflamed atherosclerotic plaque. The plaque has likely ruptured and embolized to the distal vasculature and occluded it causing tissue ischemia and infarction
48
What would you expect to see on his ECG if patient has had anterolateral myocardial infarction?
* ST elevation in all of the precordial leads
| * Also see ST depression in the lateral leads which correspond to this patient's infarction
49
Treatment for patient with MI and explanantion
- Oxygen: will increase oxygen saturation and oxygen delivery
- nitrates (nitroglycerine): increase oxygen saturation and oxygen delivery by dilating vessels
- Beta-blockers: Bind and inhibit β1 receptors in the heart -> cause heart to slow down (nodal cells) and decrease contractility (myocytes)
- Morphine: pain inhibitor and decreases sympathetic tone
- Aspirin: Used as an antiplatelet (not analgesic)
50
What is causing the pain in an MI?
- Ischemic pain due to inadequate oxygen supply to the heart during this embolic event. The oxygen-deprived myocytes start to die and release chemicals that trigger myocardial nociceptors and cause pain peripherally.
51
how do beta-blockers reduce chest pain
- Used to treat arrhythmias because it has chronotropic and inotropic effects
- Blocking β1 receptors at the level of the myocytes causes decrease of Ca++ influx into the cell through L-type Ca++ channels, Ca++ efflux from the SR and influx through the RyR2 channels.
- Results in decreased contractility, negative inotropy, and decreased conduction--> the heart is not having to work as hard anymore and its' oxygen requirement is reduced--> less of an ischemic effect on the myocytes
52
How do nitrates help with pain from MI?
- what is it
- how does it work?
- why is it used with BB?
- contra indications? why?
- vasodilator
- Causes dephosphorylation of myosin light chains, allowing for relaxation--> relaxation of arteries and veins--> increases oxygen delivery
- Oxygen and nitrates improved O2 delivery and BB reduced heart activity, thus oxygen demand on the heart is decreased--> reduces ischemia--> reduces ischemic pain--> treats angina
- low BP and HR-> could decrease peripheral resistance and allow for venous pooling due to vasodilation which can lower BP further.
53
How do Dihydropyridine calcium channel blockers
help with pain from MI?
- site of action
- distinction
- would you used this during heart failure?
- example of this kind of drug
- Site of action is L-type Ca++ channels in the periphery
- Be able to make a distinction on whether you would need a Ca++ channel blocker that acts on the heart to slow arrhythmias or a CCB that act on peripheral vessels to effect oxygen delivery.
- NOPE--> They can cause an increase of volume retention in the interstitium leading to venous blood pooling which can be problematic in a patient with CHF
- amlodipine
54
How does patient transition to heart failure after an MI?
- stunned myocardium from the ischemic event, so his cardiac function isn't as effective.
55
Why is dual anti-platelet therapy important in person who just got stents?
- drugs commonly used
- Why?
- when drug-eluting stents are deployed into the coronary vasculature are at high risk for INSTANT stenosis and patients can develop complications to the procedure where a very rapid development of thrombus occurs within the stent.
- When 2 or more anti-platelet drugs are used in dual anti-platelet therapy, the risk for that instant stenosis is minimal.
- The most commonly used dual antiplatelet therapy is Aspirin and Clopidogrel
- Aspirin: Reduces the formation of platelets by blocking the production of thromboxane (TXA2) by COX
- Clopidogrel (P2Y12 Receptor Antagonist): Inhibits the activation of platelets/ platelet aggrigation by binding the ADP receptors (also known as P2Y12 receptors)
56
Compensatory mechanisms that the body utilizes in response to HF
- overview
- RAAS
- pre-load significance
- ↓ output → ↑ sympathetic tone, start utilizing the RAS system, & also some anti-diuretic hormone coming in to help
- RAS system: Metabolic compensation processing, ↑ circulating volume → ↑VR → ↑ Pre-load
- ↓ in contractility → compensatory ↑ in pre-load to allow a sustenance (increase) of stroke volume
57
Drugs needed before discharge of patient with MI who went into heart failure?
- aspirin, metoprolol, atorvastatin, clopidogrel, & ACE inhibitor or ARB
58
Atorvastatin
- MOA
- Kind of inhibition
- How does it change lipid profile?
- HMG CoA reductase inhibitor -> preventing more cholesterol formation & this will also ↑ expression of LDL receptors, which will ↑ clearance of LDL
- Competitive inhibition
- ↓ LDL and also ↓ oxidation of LDL, which comes from anti-inflammatory properties that HMG CoA reductase inhibitors -> ↓ plaque
59
Difference between ACE and ARB
- final effects? why?
- importance of vasodilation
- ACE inhibitors block angiotensin I from being converted to angiotensin II by inhibiting angiotensin converting enzyme; ARBS blocking angiotensin II from binding to AT1 receptors and causing release of aldosterone
- Blocking aldosterone secretion & the downstream effects of that → ↓Na retention so ↓BP & volume so overtime, vasodilation & ↓ sympathetic tone → ↓preload & afterload
- When there is extra volume and vasoconstriction it causes ↑Pressure → damage of organs
- Vasodilation or releasing fluid by antagonizing aldosterone & sodium retention relieves some of the pressure on the system overall → ↓ necrosis, fibrosis, & things related to tissue damage
60
At level of myocardium what effect to ACEs have?
| - is it direct or indirect effect?
- ↓ remodeling--which is thought to play a significant role in the cardiovascular benefit in the long term management of heart failure
- BOTH; Direct: Fibroblasts have AT1 receptors, so angiotensin can directly bind to fibroblasts to produce collagen; Indirect: ↓ turbulence, ↓ afterload, ↓ pressure that the ♡ has to pump against → effect on remodeling
61
Side effects of ACE inhibitor
- causes dry cough
62
Why are BB used in heart failure?
- regular mechanism
- kidney effects
- ↓ inotropy, ↓ HR, ↓ work, ↓ O2 requirement
| - Beta receptors on kidney too so by antagonizing those you antagonize renin release directly
63
How can you tell whether pts cough is due to ACE inhibitor or dx?
- If you tell him to cough & basilar crackles clear means there is Atelectasis which is a microcollapse of alveoli that tends to occur in the bases typically when someone doesn't have an adequate inspiratory effort
64
How do you treat patient with CHF who had a weekend full of salt? Why?
- example
- Administer diuretic because Volume overload so you need to get rid of it to reduce pre-load and after load
- Furosemide--loop diuretic
65
Vasodilators for CHF
- why?
- where do they target?
- specific ones?
- hydralazine and calcium channel blockers that have higher affinity for the arterioles affects both pulmonary congestion and cardiac output
- nitrates have higher affinity for the venules
- ACE inhibitors considered a mixed vasodilator
66
How do you know when to pull back on diuretic?
- Look at electrolytes: significant decrease in potassium, sodium
- blood pressure, renal function; diuretics are going to cause not only a reduction in preload and volume in general, but they also reduce afterload, so you're gonna have decreased perfusion to kidneys, so you may begin to see improvement in the renal function as you treat the heart failure but then all of a sudden, renal function starts to drop again because of the volume; you've overshot, now the patient is hypovolemic and relatively intravascularly depleted, and that can lead to kidney failure.
67
natriuretic peptides
| - what do they do?
- increase vasodilation, decrease blood pressure, decrease sympathetic tone, decrease aldosterone, all of these things; and increase diuresis at the same time because it's a combination pill with an ARB, so you're still blocking AT receptors and the RAAS pathway
- used in replacement of ACE inhibitors
68
Neprilysin inhibitors
Neprilysin Is normally breaking down the natriuretic peptides, so when you inhibit that, you get an increase in your natriuretic peptides
69
Nitroprusside
- what is it? where does it work?
- effects?
- vasodilator that works on both venules and arterioles
| - reduce afterload and preload
70
inotropes
- what is it?
- Digoxin
- Dobutamine
- Milrinone
- deals with contractility of the heart
- cardiac glycoside, acts at the Na K ATPase
- acts at B1 receptors as an agonist
- causes vasodilation, increases contraction
71
Milrinone MOA
- inhibits Phospho DiEsterase III->inhibits cyclic AMP degradation->increase calcium->causes contraction (positive inotrope) in cardiac myocytes
72
Minoxidil
- what is it?
- how does it work?
- vasodilator
| - potassium channel opener, it stabilizes the cell
73
Treatment of patient with heart failure with EF <30%?
- defibrillator placed or biventricular pacemaker with defibrillator capabilities
74
how to treat HF with preserved EF?
- Diuretics implicated first, then just manage the other symptoms related to pt disease (so treat their HTN, manage their angina, etc.)
- Switch her from ACE inhibitor to ARB because clinical data says to
Unit 6: LGS
flashcards
Decks in class (10)
# Cards
