Week 3 Flashcards
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
Q
What effect might the beta blocker have on their ability to exercise?
- could the effect on BP just be delayed?
A
- 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
Q
Beta 1 vs Beta 2 antagonist drugs
A
- 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
Q
Difference of local metabolites build up in static vs dynamic exercise
A
- 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
Q
most rapid compensatory mechanism for high BP?
- how does it work?
- what does it do?
- can it go the other way?
A
- 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
Q
chronic compensatory mechanism for increased BP?
- describe the pathway
- any other ways for renin to be activated?
A
- 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
