Block 1 Cardiovascular-Muscle
Question: I am reviewing the Cardio 5 lecture and you mention how atrial stretch receptors offset a decrease in sympathetic activity of the heart. I am having trouble understanding how the atrial stretch receptors would even be activated if there was a drop in BP due to decreasing sympathetic activity.
Additionally, I am having trouble understanding how the vasodilation due to ANF/atrial stretch actvn and the increase in heart rate due to atrial stretch actvn work in tandem to reduce venous return and thus atrial stretch.
Answer: To answer both, you need to remember that the atrial stretch receptors and ANF are released when the right atrium is being stretched, indicating a large increase in venous return. The goal is to clear the additional volume. Increasing heart rate certainly helps to do this, as does vasodilation and increasing urinary output. Increases in heart rate increase cardiac output, which lowers the amount of blood pooling in the large veins and right atrium. Venous vasodilation increases venous compliance, and increases blood storage in the periphery (so less blood is returning to the heart). Arterial vasodilation reduces afterload, thus permitting more cardiac output. I think of the right atrial systems as serving to offset potential congestive heart failure due to a lagging right heart.
These physiological changes elicit conflicting changes in arterial blood pressure: an increase in heart rate tends to increase it, while decreasing preload and afterload tends to decrease it. Changes in arterial baroreceptor activity resulting from right atrial stimuli will induce baroreceptor responses. Overall, the influences of atrial and arterial baroreceptors (and ANF release) produce an integrated response. Neither response works in isolation.
Question: Cardio 6, lecture notes p. 5: In figure C below, showing hypoproteinemia, from what I understood, it is showing that hydrostatic pressure on the arterial and venous ends increased. But in the notes about hypoproteinemia on p. 6, it only mentions that hypoproteinemia lowers the concentration of plasma proteins, and therefore, lowers plasma oncotic pressure. Why would hypoproteinemia also increase capillary hydrostatic pressure?
Answer: I am not sure why the graph is drawn the way it is. The balance between plasma hydrostatic and oncotic pressures are altered, but absolute hydrostatic pressure should not go up.
Question: A question on the hearts of athletes vs. someone with high heart rate: while both become hypertrophic, what is happening that prevents an athlete’s heart from becoming stiff, while someone with high heart rate’s heart does?
Answer: From my reading, the physiology is not clear. This could be related to the different stress placed on the ventricle under the two conditions. In exercise, ESV is low, while ESV is high with hypertension. The isovolumetric contraction is shorter during exercise than in people with hypertension. All of these differences could contribute to molecular changes in the ventricular wall.
Question: I just have a quick question about some control mechanisms in the cariovascular system. In control 1, you said that if we were exercising, we would want the sympathetic nervous to act on the Beta 2 receptors to cause vasodilation. This would allow more blood flow to skeletal muscles, increasing the amount of ATP and oxygen that circulates through the body. My question is concerning when your body goes into shock, you want vasoconstriction instead so that more blood perfuses to the brain instead of skeletal muscles. You said that in shock, the adrenal medulla would have a huge release of Epinepherine, enough to even act on the alpha receptors, resulting in vasocontriciton. But, wouldn't the epinepherine in the blood be so high that it would also act on Beta 2 receptors in the arterioles, skeletal muscles, and abdominal viscera, causing vasodilation? Just confused on this mechanism!
Answer: You are correct that in the case of shock, both alpha and beta receptors are saturated with transmitter. However, if alpha receptors are fully bound with norepinephrine or epinephrine, the second messenger system activated predominates, and vasoconstriction occurs. Vasodilation only occurs when the saturation of beta-2 receptors with transmitter is higher than for alpha receptors. This is another example of smooth muscle cells “integrating” signals that can have opposite effects.
Question: What is the difference between V (velocity of blood flow) and Q (flow rate)?
Answer: Flow rate is the amount of fluid ejected from a ventricle per unit time (L/min). Velocity refers to how rapidly the fluid moves (in mm/min). Another term for fluid velocity is “flow rate”; Q is normally referred to as "flow".
Question: So another way of looking at this is that Q is related to the heart, whereas V is related to blood?
Answer: Not really, as both refer to blood. More contractility will increase both Q and V. These are just two different physics measures, one related to the amount of blood ejected and the second to the speed at which is ejected.
Q=amount ejected per unit time
V=velocity at which it is ejected.
Question: I know flow in and out of the heart must be exactly matched otherwise you have blood pooling, but how is this always a bad thing? I understand that standing up means a drop venous return and then CO, but what about when the veins widen to act as a reservoir for blood? As the veins are widening the blood is pooling and blood returning to the heart wouldn’t match CO.
Answer: Normally 90% of the blood is in the systemic circulation. However, if there is a pumping mismatch, the normally distribution of blood changes, leading to changes in capillary pressure and edema. We will get to this later in the course.
Question: If the density value increases in the Reynolds number equations then wouldn’t the viscosity value also increase? Doesn’t an increase in hematocrit to make the blood more viscous also make the blood denser?
Answer: Not really, as red blood cells like most cells are mostly composed of water. The density of the blood does not change much with an increase in hematocrit.
Question: In the notes for the skeletal muscle lectures, you say in slide 10 and the bottom of page 4 that “after the power stroke is complete (and the configuration of the myosin molecule has changed), the myosin is no longer attracted to actin and the two molecules separate.” I’m not seeing how this is the case because the two proteins remain stuck together without ATP (like in rigor mortis).
Answer: This is the effect of ATP—the “lack of attraction” is due to ATP binding.
Question: Do white muscle fibers typically have a greater number of creatine phosphate molecules floating around? If they use ATP faster, I would think they would build up more of a storage pool than red fibers when relaxed, so they can contract for as long as possible.
Answer: This does happen.
Question: Also in the notes on page 4, you say that actin and myosin will bind strongly is they are placed in a solution with ATP and magnesium. We didn’t really discuss magnesium all that much in lecture. What is its purpose?
Answer: This is not so important for the class, but magnesium stimulates calcium re-uptake by the calcium-activated ATPase of the sarcoplasmic reticulum .
Question: Why does aortic stenosis cause the S1 sound to get larger rather than the S2 sound?
Answer: Neither the S1 or S2 heart sounds get larger during aortic stenosis. Instead, a new heart sound appears during ventricular systole. Aortic valve stenosis causes a murmur, and not a gallop.
Question: I had a question regarding the calcium induced calcium release mechanism in cardiac muscle cells. Why is it necessary for calcium to come from the outside and bind to the ryanodine receptor? Is there a specific reason as to why calcium cant just come from the outside and bind to the troponin directly?
Answer: This is a good question. Experiments have shown that a sudden transient in Ca2+ triggers the opening of the Ryanadine receptor. The Ryanodine receptors are located near the L-type calcium channels in the sarcolemma, so a sudden transient in Ca2+ occurs in their proximity during the cardiac action potential. This causes the release of a lot of Ca2+ from the sarcoplasmic reticulum.
Note that only a small amount of Ca2+ enters the sarcoplasm at the cell surface; the large amount of Ca2+ needed to saturate troponin comes mainly from the sarcoplasmic reticulum. So, the answer to your question is that the amount of Ca2+ entering from outside the myocyte is not sufficient to cause contraction. The only reason that the Ryanodine receptor senses the Ca2+ entry is because of proximity to the L-type Ca2+ channel. Most of the troponin is away from the sarcolemma, deep in the cell.
Question: For the problem about venous pooling during quiet standing. Why is the cause due to venous compliance? Google search of venous insufficiency says that people with this condition have issues with long periods of standing due to high venous pressure not allowing blood to return to heart.
Answer: The pressure that is developed in the leg veins during quiet standing is related to the amount of blood in the vessel and its compliance. High venous pressure is a result on the forces in play, but is not a causative factor. Compliance of the vessels determines the driving force to return blood to the heart. So, venous pressure is a result of the pooling, but is not the cause! The question was worded carefully to capture this.
Question: I am a little confused about a question from the first homework assignment. I talked to my TA about the venous complience question and she thought the best answer was venous pressure. Is that wrong because there is essentially no pressure in the veins?
Answer: Venous compliance is a property of the vessel wall. The only factor listed in the question that changes the property of the wall is venous smooth muscle tone. Blood pooling in veins would alter the pressure in the vessel in accordance with its compliance, but would not change the compliance.
Question: Question on the Vascular Function Curve: If the pressure becomes negative when the pump is turned up, and the vasculature begins to collapse, why does the cardiac output plateau and not decrease? Or does it after the pressure becomes more negative?
Answer: It probably would if the negative pressure was too high. At moderate rates of negative pressure, increased flow balances the collapse of the arteries.
Question: The lecture notes state that phosphorylation of phospholamban results in enhanced activity of SERCA. I am under the impression that inhibition of SERCA by phospholamban occurs when PLB is coupled to SERCA. Does this mean the phosphorylation of PLB causes dissociation from SERCA?
Answer: This is essentially correct. Phospholamban inhibits SERCA, and the second messenger cascade triggered by sympathetic stimulation causes phospholamban to dissociate from SERCA so SERCA operates more efficiently.
Question: I am reviewing my muscle notes, and in the skeletal muscle notes it talks about the use of ATP to help bring the myosin heads because to original configuration after a power stroke. However, in the last page of the notes (page 13) on the section of relaxation of muscle, it states that no active expenditure of energy is needed for relaxation to occur at normal length. Wouldn't ATP be needed to used to bring myosin back to original configuration in order for relaxation to occur thus use of energy??
Answer: This is definitely true, but ATP is not required after the myosin heads separate from actin. The point is that the process of relaxation takes a lot less energy than contraction, as after the myosin heads separate (the end of contraction), no energy is required in the process.
Question: I have a question about myocardial oxygen demand. I have read that increasing afterload will increase myocardial oxygen demand, but I don't understand why. Increasing afterload decreases cardiac output since the stroke volume is decreased, so isn't this contradictory; shouldn't myocardial oxygen demand be lower if cardiac output is lowered?
Answer: The myocardial oxygen demand increase associated with increased afterload is mainly related to an increase in potential energy (work done prior to opening of the aortic valve). Cross bridge cycling and ATP usage is occurring to generate enough pressure to open the aortic valve. This requires a lot of energy, which is essentially wasted energy since it does not directly result in blood ejection.
Question: Why would maximum sympathetic stimulation cause RVR to go up and decrease the slope of the curve? Wouldn't maximum sympathetic stimulation also involve a big release of epinephrine acting on beta 2 receptors to dilate arlerioles and give a lower RVR?
Answer: Most arterioles lack Beta-2 receptors, and vasoconstrict when sympathetic nervous system activity is high. Moreover, maximal sympathetic stimulation likely causes the release of enough epinephrine to bind to alpha-receptors, and that effect predominates. Maximal sympathetic stimulation undoubtedly causes TPR to rise.
Question: I had another question about the Tophat homework question asking about the Wiggers diagram. I know one of the answers is the end of the v wave, but I'm unsure about the Ca2+ channels. I wanted to say they are closed because atrial depolarization doesn't happen immediately after t wave, but aren't some Ca2+ channels always open on aut rhythmic cells?
Answer: Ca2+ channels are open in the SA node autorhythmic cells during the action potential, which is the event that triggers atrial contraction. This will occur just before the P wave.
Question: Why does the aortic valve open and close at 2 different pressures(according the the PV diagram). If the only force mediating the opening/closing of the valves is the peripheral resistance, shouldn’t the aorta open at the same pressure?
Answer: The key is that the relative difference in pressure across the valve determine whether it is open or closes. This is easier to see on the Wiggers’ diagram. The aortic valve opens as soon as the ventricular pressure exceeds aortic pressure. It closes due to the retrograde movement of blood from the aorta back into the ventricle. This closure process takes a few milliseconds (just due to the mechanical properties of the valve), and ventricular pressure is changing quickly during this period. Thus it looks like ventricular pressure is quite a bit lower than aortic pressure before the valve closes.
Question: I was question on Dobutamine question's answer. The answer key states that C is the answer, but I put E which says the D and C are true. Answer D was states that probability of arrhythmia is reduced on beta blocker. Isn't this true which was discussed in recent PBL. Since beta blocker does reduce heart rate, which can be used to help control arrhythmia because tachycardia prevents appropriate amount filling before contracting which reduces cardiac output. Granted, the use of beta blocker is more effective with reducing end systolic volume, but I don't see why you can't consider D as well since it would reduce chance of inducing arrhythmia.
Answer: Dobutamine is an AGONIST, not an antagonist — it stimulates beta receptors. It is the opposite of a beta-blocker. Thus, it definitely increases the chances of arrhythmia. It increases contractility, so end systolic volumes are lower.
Block 2 Respiratory
Question: I have a question about alveolar collapse and alveolar structure in general. When inspiration occurs, does the alveoli increase in radius appreciably as air fills the sac? Additionally, when an alveoli collapses, and air flow is rerouted into the larger alveoli, do these alveoli collapse as well due to higher than normal flow? Or does the body just prevent big inspirations from occurring? Lastly, how are collapsed alveoli clinically treated?
Answer: The volume of alveoli does increase during inspiration, resulting in negative pressure in the lungs.
I am not sure what you are getting at in the second question: Additionally, when an alveoli collapses, and air flow is rerouted into the larger alveoli, do these alveoli collapse as well due to higher than normal flow?
The Hering Breuer reflex that we discussed on Monday helps prevent lung overinflation.
NIH has a nice page on atelectasis, or lung collapse: https://www.nhlbi.nih.gov/health/health-topics/topics/atl
Question: Is the residual volume a function of how well your respiratory muscles can generate force? Would you be able to decrease the residual volume through strengthening of the respiratory muscles? Additionally, would an olympic athlete be able generate greater vital capacity through training the intercostal muscles or is the body more concerned with improving oxygen delivery(through increased hemoglobin)?
Answer: There is a small increase in inspiratory reserve volume and a small decrease in expiratory reserve volume during training. There is no appreciable change in hematocrit with training, unless of course someone trains at altitude or takes synthetic erythropoeitin.
Question: In Respiratory 1, lecture notes p. 3, it says as a first step in hemostasis, the pressure in the vessel must be decreased until a blood clot forms to seal the vessel. But then it says an early step in hemostasis is endothelin release from damaged endothelial cells which induces local vasoconstriction. I was confused since I thought endothelin would actually increase blood pressure before the blood clot has time to form.
Answer: Constriction occurs upstream from the damaged vessel, reducing flow to the damaged part. The key is that endothelial spreads locally and affects smooth muscle in front of the damage .
Block 3 Renal
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Block 4 Immunology
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Block 5 Gastrointestinal/Temp and Growth Regulation
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Block 6 Reproductive and Developmental Physiology
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