physiology block II Flashcards
(98 cards)
0
Q
what is laminar flow? what is turbulent flow?
A
laminar flow- blood flows in a line. makes sort of a parabola shape- blood in the middle flows faster than blood on the sides of the tube. we should expect to see laminar flow in larger vessels
turbulent flow can occur in larger vessels when we are above the critical velocity. it is NOT laminar.
1
Q
What are the characteristics of laminar flow?
A
.
2
Q
what equation summarizes the relationship between pressure, flow, and resistance in fluid systems? what determines resistance?
A
Q = (P1-P2)/R
where Q is flow, p1- p2 describes the pressure gradient, and r is resistance
R = (81/pi)* viscosity * (1/r^4)
so BIG resistance is LOW flow
small radius or high viscosity lead to big resistance
3
Q
what is the pressure flow resistance relationship in systemic circulation? what is flow?
A
Paorta- Prt atrium = total flow * total peripheral resistance
flow is vol/unit time; calculated as the stroke vol. * heart rate
4
Q
What is pulse pressure?
A
systolic pressure - diastolic pressure
5
Q
what is mean arterial pressure?
A
diastolic pressure plus 1/3 of pulse pressure
6
Q
where in the circulatory system does the greatest drop in pressure occur?
A
arterioles
7
Q
IN A HEALTHY INDIVIDUAL, how might we describe the systemic circulation? what assumption is being made?
A
Paorta = total flow * total periferal resistance (assumes that P right atrium is negligible)
or
mean arterial pressure = cardiac output * total peripheral resistance
remember that cardiac out put is
heart rate times stroke volume
8
Q
What are the assumptions made in Poiseuille’s equation?
A
- laminar flow
- rigid cylindrical tube of uniform diameter
- steady (non-pulsatile) flow
- uniform viscosity independent of velocity
9
Q
What are some basic problems with the assumptions of Poiseuille relationships as applied to the circulation?
A
blood vessels aren’t rigid, and they aren’t cylindrical (they branch). flow is pulsitile in aorta and the arteries, and we can see bolus build up in the capillaries. we can also sometimes see turbulent flow in large vessels.
10
Q
When do we see turbulent flow? What factors determine when we reach that point?
A
until the critical velocity, flow is linearly related to pressure.
above the critical velocity (reynold’s number above 2000) we see turbulence.
critical velocity predicted by Reynold’s number:
Reynold’s number = densitydiametervelocity/viscosity
(basically, things in the denominator increase momentum or speed- density, diameter, velocity; viscosity slows stuff down).
11
Q
What is a newtonian fluid? When does blood behave like one? When doesn’t it?
A
newtonian fluids have viscosities unaffected by velocity
blood behaves this way in large vessles but not smaller ones. viscosity is inversely related to velocity.
12
Q
What is cardiac output?
A
stroke volume X heart rate
13
Q
what factors determine stroke volume?
A
preload, contractility, afterload
14
Q
What is ejection fraction?
A
ejection fxn =stroke vol/ left ventricle end diastolic volume
15
Q
When does preload have the biggest effect on stroke volume? (aka high or low left ventricle end diastolic pressure
A
low volumes
16
Q
What do we use as a proxy for left ventricle end diastolic volume?
A
end diastolic left ventricle pressure
17
Q
what can we use to estimate left ventricle end diastolic pressure?
A
pulmonary capillary wedge pressure
18
Q
What are baroreceptors? Where are they located? What are their three most important characteristics?
A
baroreceptors detect blood pressure
they are located in the carotid sinuses and the arch of the aorta.
three characteristics:
they fire in response to stretching/pressure
they have a minimum and a maximum threshold
they are best at detecting changes in pressure
19
Q
Into what structure do baroreceptors relay information?
A
NTS
20
Q
What does the NTS do? (very basic)
A
stimulates parasympathetic system directly and inhibits VLM, which stimulates the sympathetic system
21
Q
What are the major anatomical and functional differences between large and small arterioles?
A
anatomically, the differences are SIZE (small <500 um) and AMOUNT of smooth muscle (larger vessels have more)
functionally, arterioles control pressure/resistance, capillaries are the sites for exchange, and venuoles are responsible for capacitance.
22
Q
What is Poiseuille’s equation?
A
Q= (delta P * pi r^4)/(L8*viscosity)
where delta p/L is the pressure drop along a length of tube L, r is the radius of the tube, and Q is the blood flow
SO
AQ is protortional to the ratio of pressure drop and resistance where resistance is kviscosity/r^4 (K is 8L)
23
Q
What is hemocrit?
A
change in the volume fraction of the red blood cells
24
Explain the Fahraeus-Lindqvist effect
Recall that overall flow in a system must remain constant, but the velocity of a given particle through a higher resistance area can be relatively fast. Red blood cells like to stay in the middle of the small arterioles/capillaries as they pass through, and flow is fastest in these areas. So, hematocri (ratio of RBCs to other stuff in the blood) is lower in these small areas than in higher areas, because the RBCs are moving faster than the surrounding plasma.
25
What are two main ways that arterioles can control tone locally?
Myogenic- stretch receptors open Ca channels when they are stretched to cause vasoconstriction
Metabolic: factors are released from tissue whose metabolic needs have changed. Includes changes in PO2, PCO2, ADP, NO, high temperature, hydrogen ions, lactate, all cause vasodilation (body's response to a tissue that is demanding more oxygen). In some cases, esp. that of purines, we seey hyperpolarization due to activation of Katp channels (makes contraction harder!)
Similarly, K from contracting skeletal muscle will be brought into the cell via K inward rectifiers and cause hyperpolarization leading to vasodilation.
26
Summarize the role of endothelial cells in maintaining arteriolar tone.
- Mechanosensitive to shear stress (friction that the blood exerts on the arteriolar walls), which causes release of nitric oxide, which causes vasodilation (think: nitro to help with bloodflow for someone with chest pain!).
- Can also release other agents- endothelin (vasoconstrictor) as well as protaglandins and hyperpolarizing factors (hyperpolarizing factors cause relaxation, obviously).
27
How do we see axial communication of vasodilation signals? why is it important?
Important so that we actually see increased flow to an area that needs it, and not just a sausage effect.
mediated through the gap juctions between the cells lining the vessels. OR through flow dependent dilation- shear stress causes NO release, which causes changes in nearby vessel regions, which cause dilation and propagation of the dilation.
28
What are the two ways that material can be exchanged across the capillaries?
Paracellular (through junctions) and transcellular (through vesicles across the cell)
29
How much O2 can 1 g of Hb carry?
1.39 g O2 theoretically- in practice, more like 1.34-1.36 g O2.
30
What are the most important factors that can shift the hemoglobin oxygen binding curve to the RIGHT (ie. low affinity)?
Increases in CO2 (Bohr effect), increase 2,3 DPG, increased temperature, increased H+ ion, increased CO
31
What is the main way that CO2 is transported in the blood?
as bicarbonate, which is made by the reaction of CO2 with H2O catalyzed by carbonic anhydrase in the RBC.
32
What should I know about the "chloride shift"? ie what is it and how does it happen?
HCO3- is exchanged for Cl- from outside the cell. this happens by an exchange protein called Band 3 (disovered at UofR
33
What is the bohr shift?
This baiscally explains why CO2 and H+ both shift the oxygen hemoglobin association curve to the right- ie. lead to a decrease in the affinity of Hb for O2. Hb is a weaker acid than HbO2, so H+ has a stronger association for Hb (the form without bound oxygen), and H+ favors unloading of oxygen from Hb.
34
What is the haldane effect?
basically, deoxigenated hemoglobin promotes CO2 transport because CO2 binds better to Hb than to HbO2.
35
What are the two classes of smooth muscle? What are some examples of each class?
multi-unit: little or no electrical connectivity between muscle cells; controled mostly by nerves. Exampes are iris, piloerector, vas derenes, trachea
Unitary: electrically coupled; propagation of APs important. the do show some spontaneous electrical activity ("slow waves") but can also be reculated by hormonal and/or neural stimulation. examples are gut smooth muscle, ureters, uterus
36
In what three ways can calcium enter a smooth muscle cells?
voltage-gated calcium channels
receptor activated calcium channels (pharmaco-mechanical coupling)
by release from the SR
37
How is calcium released from the SR in smooth muscle?
stimulus to the cell, like norepinphrine binding to an alpha adrenergic recpetor
guinine binding protine activated by stimulus binding.
G protein activates phospholipase C (PLC)
PLC hydrolyzes inactive phosphatidyl inositol bisphosphate (PIP2) to make diacylglycerol and IP3
IP3 (inositol 1,4,5 triphosphate)binds the SR membrane, triggers Ca release from the SR.
38
In smooth muscle, what happens when calcium is released into the cytosol?
Calcium associates with calmodulin
calmoduin can then activate a calmodulin-dependent myosin light chain kinase (MLCK)
MLCK phosphorylates smooth muscle myosin
myosin can no hydrolyze ATP and interact with actin
39
Where are smooth muscle contractile units anchored?
dense bodies
40
What is the major difference between the thin filaments in smooth muscle and the thin filaments of skeletal muscle?
the thin filaments of smooth muscle don't have troponin, which normally blocks myosin from interacting with actin. In smooth muscle, actin is always ready to go- muscle contraction is regulated instead by the phosphorylation status of myosin.
41
What connects unitary smooth muscle cells to each other?
gap junctions, intermediate junctions, and desmosome-like junctions
42
How is contraction terminated in smooth muscle?
myosin light chain phosphatase dephosphorylates the myosin light chain, which inhibits interactions between myosin and actin
43
what are the three classes of anti-hypertensive medications?
1. vasodilators (
2. diuretics
3. sympatholytics
44
what are the four kinds of direct vasodilators that I need to know?
calcium channel blockers, potassium channel blockers, angiotensin II inhibitors, and nitrates
45
How do calcium channel blockers work, generally?
they work by blocking calcium entry through L-type (voltage-gated) calcium channels. If calcium can't enter the cell, then we don't see calcium binding to calmodulin and subsequent activation of myosin light chain kinase and smooth muscle cell contraction. these have the potential to also have an impact on cardiac cells.
46
What are thre three main classes of calcium channel blockers?
1. dihydropyridines
2. benzothiazepines
3. phenylalkylamines
47
What class of calcium channel blockers is most selective for vascular smooth muscle?
dihydropyridines
48
How do potassium channel openers act as vasodilators?
they active atp-dependent potassium channels, leading to hyperpolarization of the cell. hyperpolarized cells keep L-type calcium channels closed, so calcium does not enter the muscle and we don't see smooth muscle contraction.
49
What does angiotensin II do?
angiotensin II causes vasoconstriction when bound to the angiotensin I receptor
50
What are the two subclasses of angiotensin II inhibitors? How do they work?
1. ACE inhibitors: inhibit the angiotensin converting enzyme (ACE), which is responsible for producing the active angiotensin II from angiotensin I circulating in the blood. Absence of angiotensin II leads to vasodilation
2. Angiotensin II receptor blockers block the interaction between angiotensin II and its receptor, which again leads to vasodilation.
51
How do nitrates work? (this one is hard)
Nitrates do a lot. Overall, they are most active on VEINS at therapeutic doses, which means that the veins will dilate and more blood will be stored in the veins and we will see a reduction in the cardiac preload.
Nitrates cause vasodilation by a cascade of events:
1. become NO
2. NO activates guanylyl cyclase
3. guanylyl cylclase increases intracellular concentrations of cGMP
4. cGMP activates cGMP=dependent protein kinase (PKG)
PKG does a number of things
1. Reduce the activity of L-type calcium channels
2. limits IP3-induced calcium release
3. activates the myosin light chain phosphatase, wich dephosphorylates the myosin light chain, which prevents myosin from binding to action. that leads to muscle relaxation.
52
what are the three most important natural vasoconstrictors? How are they categorized (ie. by their source)
endothelin (paracrine), norepinephrine (neural), angiotensin II (hormonal)
53
what are the three most important vasodilators and their classifications?
epinephrine (hormonal), NO (local), acetylcholine (neural)
54
what inactivates myosin light chain kinase/calmodulin?
.
55
What is the major factor that determines the rate of blood flow to different organs of the body?
changes in the vascular resistance to blood flow to that organ.
56
explain the concept of redistribution of blood flow
redistribution of blood flow relates to the fact that the circulatory system vascular beds are essentially resistors in parallel. blood flow overall is constant, but by dramatically reducing resistance to flow in one are and increasing resistance to flow in another area, you can direct blood flow to areas that are demanding more oxygen/supplies at any given time.
57
What is the primary site of regulation of peripheral vascular resistance and the distrubution of blood flow?
arterioles
58
what are the two systemic influences on arteriolar tone?
neural control and endocrine control
59
What does sympathetic stimulation do in terms of arteriolar tone? How?
It releases norepinephrine, which binds to alpha-adrenergic receptors, which causes vasoconstriction.
60
What regions show the most intense vasoconstriction under sympathetic stimulation?
renal, splanchnic, and cutaneous circulation (the stuff you don't really need for fight or flight)
61
What are the two hormones that might be released when we don't have enough blood volume/blood pressure? What do they do in stress conditions?
angiotensin and vasopressin. they can cause vasoconstriction
62
What are the three main types of local regulation of arteriolar tone?
myogenic, metabolic, endothelial-derived substances
63
Describe myogenic regulation of arteriolar tone. How does it work?
Myogenic regulation is basically taht we see vasoconstriction in response to arteriolar stretch. Stretch receptors (aka mechanosensitive ion channels) are non-selective ion channels that open in response to mechanical stretch. They let in a ton of cations, which cause depolarization, which open calcium channels, which cause vasoconstriction. We see this myogenic response in most of the cells of the body, but it can be overridden by other regulatory factors.
64
What are some metabolic local regulators of arteriolar tone? What do they cause?
elevated PCO2, lactic acid, low pH, adenosine, extracellular potassium, decreased PO2. These cause vasodilation- these are tissues that need more oxygen supplies!!
65
Where is metabolic regulation of arteriolar tone most important?
In skeletal muscle and coronary circulation.
66
What is reactive hyperemia?
This is what happens when we see vasodilation because there has been an increase in metabolic byproducts because of vasoconstriction (so, even though oxygen use hasn't changed, the oxygen supply has gone down, and the tissue is basically asking for more blood suppy).
67
What plays an important role in mediating vasodilatory responses to ischemia in the coronary circulation?
adenosine
68
Where is PCO2 most important for regulation of arteriolar tone? What does it do? Under what conditions?
PCO2 is important for vasodilation to the cerebral circulation when respiration is depressed.
69
What are the five main endothelial-derived vasoactive substances? What do they do (ie. constrict vs. dilate)
1. Nitric Oxide (vasodilator)
2. EDHF: endotheilal derived hyperpolarizing factor (vasodilator)
3. Prostacyclin (PGI2): vasodilator
4. prostiglandins and thromobxames: both vasodilators and vasoconstricters; aspirin blocks their formation
5. endothelin: vasoconstrictor
70
What are some important contributions to vascular regulation by nitric oxide (big picture, not tiny Dirkson details)
1. low basal tone maintenance
2. mediate vasodilation for things like acetylcholine and brachykinin
3. initiates flow-mediated vasodilation
71
What is flow-mediated vasodilation? Where is it particularly important? What mediates it?
Flow mediated vasodilation is what happens when endothelial cells release more NO in response to increased shear stress due to increased blood flow. This NO causes vasodilation, which in turn causes more blood flow, constituting a positive feedback loop. this is especially important in skeletal muscle and coronary circulation.
72
What is autoregulation? In which circulations is it most prominent?
Autoregulation is when a tissue's blood flow remains constant, even though arterial pressure is changing. It is mediated through myogenic regulation, the paracrine response, metabolic response, or a combination of the three. It is most prominent in cerebral and renal circulations.
73
What is intrinsic tone? What vascular beds have HIGH intrinsic tone?
Intrinsic tone is the degree of vasoconstriction seen in the absence of hormonal or neural stimulation. A vascular bed with high intrinsic tone is normally constricted, but can show crazy vasodilation in response to vasodilatory factors. Examples of muscles with high intrinsic tone are skeletal muscle and coronary circulations.
74
What does the primary regulation of arteriolar tone in the skin? What is this regulation in response to?
the primary regulation of blood flow to the skin is neural in response to the body's thermoregulatory drive (hypothalamus)
75
How does neural regulation of cutaneous circulation work?
Three ways:
1. sympathetic stimulation leads to vasoconstriction
2. decrease in sympathetic stimulation leads to vasodilation-- cutaneous circulation has high basal sympathetic tone
3. there is a mystery peptide that seems to actively promote vasodilation.
76
What are the local effects on cutaneous circulation?
1. locally increased temp promotes vasodilation
2. locally decreased temp causes vasoconstriction
3. EXTREME local cold promotes vasodilation to fight against frostbite.
77
How is renal flow regulated? What is happening in the kidneys in terms of blood flow at rest?
At rest, the kidneys get a lot of blood flow- much more blood flow than they need based on oxygen demands- because they are responsible for filtering the blood. However, blood flow to the kidneys can be dramatically decreased by sympathetic stimulation. Interestingly, lack of sympathetic stimuation doesn't cause much vasodilation, because the kidneys have low resting sympathetic tone (they really do want a lot of blood flow at resting conditions).
78
What happens to splanchnic circulation during exercise? What effect does this have systemically?
The splanchnic tissues, which normally see a lot of blood volume, constrict dramatically. This has two important systemic effects:
1. there is an increase in total peripheral resistance
2. because the venous system of veins also constricts, especially in the liver, there is a decrease in venous capacitance and the blood that was being stored in the veins shifts into the central venous pool
79
What are the major regulators of blood flow to skeletal muscle at rest?
sympathetic control and the baroreflex, myogenic autoregulation
80
What is the most important factor controlling blood flow to skeletal muscle during exercise/stress?
LOCAL CONTROL based on metabolic byproducts, which cause vasodilation.
81
what two factors allow for the dramatic increase in oxygen utilization by skeletal muscles during exercise?
1. increased oxygen extraction
| 2. increased blood flow
82
Describe, briefly, the factors that allow skeletal muscle to meet its oxygen needs during exercise
1. Initially, metabolic byproducts lead to vasodilation
2. vasodilation leads to increased blood flow
3. increased blood flow increases the shear stress on the endothelial cells, which sense this and release NO in response.
4. NO causes lots of vasodilation- this is a positive feedback loop!
5. increased blood flow leads to increased oxygen supply
6. we also see increased oxygen extraction due to capillary recruitment (deconstrict arterioles and suddenly the capillary beds that feed off of a given arteriole can be filled- this is capillary recruitement)-- increases surface area and decreases distance that O2 has to travel
7. oxygen use causes a concentration gradient between the capillaries and the tissues with regards to oxygen- this too facilitates oxygen flux.
83
What factors facilitate oxygen extraction in exercising skeletal muscle?
1. Bohr shift (presence of H+ and CO2 shifts oxygen hemoglobin dissociation curve to the right, which promotes oxygen unloading)
2. decreased PO2 in the tissues increases the concentration difference between PO2 in the blood and PO2 in the tissues
3. capillary recruitment- blood spends LONGER in the capillaries, it increases the surface area for exchange, and decreases the distance that the O2 has to travel to find the tissue that it is looking for.
84
What is the most prominent way that the circulation of the heart responds to increased cardiac work? What mediates this response?
through metabolic vasodilation
85
what is one of the most important regulators of coronary flow? is it a vasodilator or a vasoconstrictor (unique to coronary flow in its importance)
adenosine- it is a vasodilator and metabolic byproduct
86
What is one difference between cardiac and skeletal muscle in terms of how increased oxygen demands are met (ie. what can't cardiac muscle rely on)?
cardiac muscle has very high oxygen extraction even at base, so it must rely on increased blood flow more than increased oxygen extraction at times of stress/increased demand
87
describe the three types of arteries in the brain.
pial arteries, in the pial space, which do receive sympathetic innervation. don't penetrate brain tissue but are bathed in CSF
penetrating arterioles: penetrate brain tissue
parenchymal arterioles: penetrate the brain tissue and are surrounded by astrocytes, who mediate most of the neural contact with the parenchymal arterials. relatievly high basal tone, not responsive to NE, and don't have a good collateral network.
88
What is a neurovascular unit in the brain?
neurovascular unit describes the pericytes and endothelial cells plus their basal lamina. this group is covered by astrocyte end-feet
89
How/why does BOLD MRI work?
basically, BOLD can be used to detect active areas of the brain based on where it sees an increased level of oxyhemoglobin. active areas have increased oxyhemoglobin levels compared to inactive areas for two reasons. First, there is a metabolically coupled increase in blood flow to that region. However, oxygen extraction is not as high as you would expect based on cerebral glucose metabolism, and is not proportionate to the increased blood flow, because the astrocytes provide the neurons with energy generated by anaerobic methods. Even though oxygen consumption IS going up, it is not going up as much as blood flow to that area of the brain is, so we still see an overall increase in the content of oxyhemoglobin in those active regions of the brain.
90
What does caffeine do to the brain? What happens during caffeine withdrawal?
Caffeine causes vasoconstriction of blood vessels, decouples blood flow from metabolic need, and enhances neural activity by preventing repression of neurotransmitter release by over active neurons (ie. adenosine-linked repression of neurotransmitter release). Caffeine withdrawal takes away the vasoconstriction, leading to increased blood flow, and restores metabolic demand.
91
What are the four factors that can have an effect on cerebral blood flow?
1. metabolic factors
2. neuronal control- extrinsic through sympathetic stimulation, though this isn't the most important pathway in a ahealthy individual, and intrinsic trhough communication between the neurons in the brain and their blood supply, mediated by the astrocyes and endothelium.
3. carbon dioxide levels- increased carbon dioxide levels cause dramatic increases in cerebral blood flow
4. autoregulation
92
What is the main factor the mediates autoregulation in the brain? How does it work?
the myogenic response is most prominent in the cerebral circulation. basically, increases in shear stress and pressure lead to the release of vasoactive substances which cause the endothelial cells to release NO. NO stimulates guanylyl cyclase, which increases cGMP, which activates myosin light chain phosphatase (among other things) and leads to vascular relaxtion.
93
what happens at the upper limit of autoregulation in cerebral blood flow?
autoregulatory breakthrough becuase pressures are too high to resist, leading to the possibility of hemorrhage and edema (which is very dangerous, since brain can't really swell much without damaging tissue). examples include eclampsia and altitude sickness.
94
What happens when we reach the lower limit of the autoregulatory abilities for cerebral blood flow?
we dilate, but eventually we can't dilate anymore and we have to try to compensate by increasing oxygen extraction. we can only increase oxygen extraction so much, though (about 60%), so at some point we'll start to see ischemia and tissue death :(
95
what forms the blood-csf barrier? how does that work?
csf is formed by the coroid plexus, which is very leaky to the interstitial fluid of the brain. however, tight junctions of epithelial cells in the coroid plexus prevent csf from mixing with blood.
96
what forms the blood brain barrier? how does it work?
blood brain barrier is formed by endothelial cells that are connected to each other with tight junctions that prevent the flux of ions and proteins and cells into the brain. these endothelial cells use active transport to spit out waste into the bloodstream and have no fenestration and low pinocytosis.
97
What proteins make up the tight junctions of the blood brain barrier?
claudin, junction adhesion molecules
