Block 1 Cardiovascular-Muscle
Question: In Cardio 5 you mentioned how an increase in blood pressure causes Na channels to open which eventually promotes vasoconstriction. However, later you said that NO created as a result of shear stress eventually promotes vasodilation. To me, this sounded like a bit of a contradiction. Is the difference simply in the nature of the "stress" applying pressure to the vessel walls? Is it that the Na channels open as a result of higher perpendicular pressure and that NO is synthesized simply by blood grazing the walls of the arteries and not directly applying a perpendicular force? Or are these responses situation specific?
To go along with this, why is it useful for the vessels to dilate during shear stress?
Answer: First of all, pressure and sheer stress are two different physical properties. Pressure is a force perpendicular to a surface, while sheer stress is parallel to it. In other words, pressure pushes the vessel wall outwards, while sheer stress is caused by blood dragging along the endothelial surface.
Increased perfusion of a vessel can cause both increased pressure and sheer stress. You are right that these can have opposite effects. The two offsetting effects tend to keep each other in check.
The pressure effects (myogenic autoregulation) tend to keep flow stable if blood pressure suddenly goes up or down. The sheer stress effects tend to facilitate dilation of arteries that are being perfused heavily.
Question: A question from Cardio 7: Exercise and hemorrhage both result in increased sympathetic activity, so why are circulating epinephrine levels so much higher during hemorrhage? Are there specific effects on adrenal secretion that are unique to hemorrhage?
Answer: Note that there are two very different triggers for increased sympathetic nerve activity during the two situations. During exercise, central command and feedback from muscle afferent fibers causes a moderate alteration in sympathetic nervous system activity. In hemorrhage, there is a decreased activation of both atrial and arterial baroreceptor afferents, which causes a huge increase in sympathetic nervous system activity. The adrenal medulla is driven very hard to release maximal epinephrine during hemorrhage as a result of the strong stimuli present.
Question: I was wondering what is the importance or relative advantage of concentrating Angiotensin-converting enzyme in the lungs?
Answer: This is simply because the lungs get 100% of the blood volume each time it moves through the circulation. Other organs only get a fraction of the blood volume. By placing ACE in the pulmonary circulation, ANG-2 is formed quickly after the kidney releases renin.
Question: In Cardio 7 you mention that TPR decreases due to an increase in the number of vascular beds during exercise. This decrease in TPR is said to be the cause of the large drop off in diastolic pressure. I understand that pressure would drop (P=QR), however I do not understand why pressure during systole would not drop due to this decreased TPR as well.
Answer: The wording was a bit unclear. Technically, if BP increases then afterload increases. The technically correct explanation is that TPR drops during exercise. However, since BP is TPR*CO and CO increases 4-fold, then afterload increases slightly even though TPR decreases.
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 .
Question: Does a low hemoglobin saturation mean there's less saturation because more of it is being delivered to the tissue, or does it mean there's less saturation because there just isn't enough O2 to cover all the binding sites, let alone be delivered to the tissue? For example, if PO2 in the blood returning from tissues is decreased to 30 mm Hg instead of the normal value of 40 mm Hg, the hemoglobin saturation will be decreased. But is it decreased because there has been more unloading of O2 to the tissue, or is it indicative of inadequate ventilation?
Answer: In terms of HB saturation, the alveolar pO2 is the main determinant for arterial blood, and unloading to tissues is the main determinant in venous blood. Usually arterial Hb is near 100% saturated with oxygen unless there is a serious pulmonary problem.
Question: I have a question on Problem 7, Part B from the 2016 version of Exam #2. I understand that to calculate alveolar ventilation in Part C, one must subtract both the average person’s headspace (150 mL) and the volume of the snorkel (100 mL) from the total breath volume (600 mL), then multiply by the breathing rate (15 bpm). In calculating total pulmonary ventilation in Part B, I understand that one should not subtract the dead space from the total breath volume. However, I am unclear as to why one should not subtract the volume of air in the snorkel since that volume is not part of our pulmonary system, suggesting it wouldn’t be included in total pulmonary ventilation. I’d appreciate your clarification on this.
Answer: Pulmonary ventilation is the amount of air brought into the lungs. That would include the volume of air in the snorkel. This is why it is not subtracted.
Question: I had a quick question about hemoglobin and PO2. I understand that arterial and venous blood have very different PO2 levels, yet they have similar blood oxygenation. Generally, when talking about PO2, are we only talking about the partial pressure of O2 in the plasma, excluding that inside the RBC's? I was confused because I thought when you say PO2 of the blood, it would take into account the O2 in both the plasma and inside the RBC's, bound to hemoglobin.
Answer: PO2 applies to the amount of oxygen dissolved in the plasma. It does not include O2 attached to Hb.
Question: Why is it that your chemoreceptors don't autocorrect the PCO2 in respiratory acidosis/alkalosis, like they do in metabolic acidosis/alkalosis? When you have respiratory acidosis, due to hypoventilation, the PCO2 is high, and H+ increases. Wouldn't the chemoreceptors sense the high H+ levels in the blood and cause the person to hyperventilate, to drive down the PCO2 levels?
Answer: They do elicit compensation. However, there is a complexity in that the correction may also provide negative feedback. Take as an example metabolic acidosis. The drop in plasma pH will activate peripheral chemoreceptors, inducing hyperventiulation. In turn, this lowers pO2 and pCO2, which tends to shut the chemoreceptors down. The fact that peripheral chemoreceptors respond to changes in pH, pCO2, and pO2 can result in a complex response pattern to changes in one of these parameters.
Question: I am reviewing Respiratory 5 and I was wondering the physiologic mechanisms that lead to the differences in HCO3- between respiratory and metabolic disturbances? I am having trouble understanding the physiologic reason leading to the discrepancy in HCO3- that determines whether a disturbance is metabolic/respiratory.
Answer: The chief difference depends on whether CO2 is being manipulated or H+ or HCO3- are being changed.
CO2 + H2O < -- > H2CO3 < -- > H+ + HCO3-
In metabolic acidosis, H+ is being added to the plasma, so HCO3- goes down via mass action. In respiratory acidosis, CO2 is being added so HCO3- increases.
In metabolic alkalosis, HCO3- is being added to the plasma, so it increases and H+ goes down. In respiratory alkalosis, CO2 goes down so HCO3- also declines through mass action.
HCO3- changes in opposite ways during respiratory and metabolic disorders. This is the key indicator to evaluate.
Question: You mentioned how the blood in the chambers of the heart itself was not enough to provide adequate perfusion to the tissues of the heart and we have coronary arteries to solve this. What is the situation for the lungs? Can they get oxygen from the alveoli inside them or do they also have a separate vessel providing them with nutrients?
Answer: The lungs mainly get O2 through the pulmonary circulation. The systemic circulation only perfuses the outer 1/3 of the lungs.
Question: You stated that you can still breathe with the diaphragm even with a T1 spinal transection, but how is this possible? Do you not need the external intercostals for inspiration? Or are the intercostal muscles only used for greater than tidal volume ventilation?
Answer: Only the diaphragm is needed to meet minimal oxygen demands. Diaphragm contraction pulls air into the base of the lungs. If the intercostals are paralyzed, then expiration is via passive recoil.
Question: How would transpulmonary pressure be affected, if at all, with deeper ventilations?
Answer: During very deep breaths, compliance (and transpulmonary pressure) decline.
Question: I calculated the pH based on HCO3- and pCO2 to be 7.3, which is exactly the given. For 2, based on those two values pH comes out to 7.36, which is actually closer to normal than the 7.33 in the problem. Unless I’m calculating pH incorrectly (6.1 + log(HCO3-/(.03*pCO2))) would that not signal lack of compensation?
Answer: When thinking about whether compensation occurred, you need to consider the primary cause of the disturbance, and whether other values correspond. For example, if pH is 7.3, pCO2 is 30, and HCO3- is 13, then an individual has partially compensated metabolic acidosis. How do you know? pCO2 is low, and HCO3- is very low, indicating that respiratory compensation must be taking place. This has to a metabolic acidosis, since bicarbonate is low. The fact that pCO2 is also low is the hint that compensation is occurring. You need to be able to predict the HCO3- that is normal at different pH and PCO2 levels to make the determination.
Question: In Respiratory 1, the logic behind heparin production was that the slow velocity of blood through the pulmonary system needed anticoagulation. However later in the lecture, its said that the pulmonary system has a high velocity. Am I misunderstanding something?
Answer: The small vessels in the lungs get perfused with blood that came from the systemic venous circulation. Because of gravitational effects, that blood could have remained in the veins for some time before returning to the right heart and being pumped into the pulmonary arteries. Clots can often form in the venous circulation, and when they do they lodge in small pulmonary arteries, the first small arteries they move through. So, the slow movement is not in the pulmonary arteries, but in the systemic veins, particularly those in the lower body.
Question: I had a question regarding the extrinsic and intrinsic pathway, how much in depth do we need to know about them? What are the major differences between them?
Answer: As mentioned in class, there is no need to learn all the factors. The intrinsic pathway does not require any factors that are not in plasma for initiation; clotting is triggered by the exposure of collagen in the wall of large blood vessels. The extrinsic pathway requires a factor released from damaged vessels for activation. The main point is that there are two pathways for initiating clotting, and both have to be knocked out to abolish clotting. They merge into a common pathway, and dysfunction of elements of the common pathway also prevent clotting.
Question: I wanted to ask you about the questions involving spinal transection. Are the locations of the particular regions and their associated function present in the lecture notes? I was only able to find the diaphragm, the intercoastal muscles and the abdominal muscles. What are the other regions we should be aware of/ where can we find them.
Answer: The only other thing you need to know is that the airway muscles are controlled by brainstem neurons with axons in cranial nerves.
Question: In the slide demonstrating transpulmonary pressure, the volume of lung goes from 0 to 0.5L, I take this as normal tidal volume. If a person is using ERV and IRV during breathing, lung volume can change appreciably, and how would alveolar pressure, pleural pressure , and transpulmonary pressure change under such condition?
Answer: With deeper breathing, alveolar and pleural pressure get more negative, and the two balance so transpulmonary pressure stays about the same. This can change a bit during maximal inspiration when lung compliance becomes starts to change, but this applies across the majority of inflation volumes.
Question: For the first question on exam 3 from 2014, could you explain why the last three parts are compensated, uncompensated, and compensated? It seems the pH values deviate too much and the bicarbonate values deviate too little for 2 and 4, and vice versa for 3. For 2, would the PCO2 value indicate hyperventilation as a compensatory mechanism?
Answer: In severe pH disturbances, compensation may only be partial. In #4, with a pCO2 of 60, pH should be 7.2, and the fact that it is 7.3 shows compensation.
IN #2, a HCO3- of 16 should also be associated with a pH of ~7.2, and thus respiratory compensation is occurring (hence a pCO2 of 29).
Question: Internal intercostal muscles are involved in active expiration, are external intercostal muscles active in every breath, or are they only activated in heavy inspiration?
Answer: The external intercostals may be slightly engaged during tidal breathing, but they are not heavily engaged until breathing is deeper. The intercostals are not needed for survival: just the diaphragm.
Question: I know that the intrinsic pathway of the coagulation pathway is activated when blood is exposed to a foreign substance such as a test tube. So for a hemophiliac who has a factor of their intrinsic pathway missing, would their blood clot not when placed in a test tube?
Answer: Hemophilia is usually a deficit in the intrinsic pathway, while clotting in a tube is via the extrinsic pathway. Hence, a hemophiliac’s blood would clot in a tube.
Question: If hematocrit suddenly dropped but the amount of oxygen stayed the same, would the excess oxygen dissolve completely in the plasma or would it stay as oxygen gas?
Answer: If hematocrit drops, then the amount of oxygen in the blood drops proportionally. There is a limited capacity for O2 to dissolve in plasma.
Block 3 Renal
Question: On page 10 of lecture one, hydrostatic pressure is shown moving inside the glowmerulus. But isn't this the osmotic flow of fluid ? Shouldn't osmotic pressure be in the opposite direction to stop the flow of osmosis?
Answer: This figure is correct, and I am not sure which pressure you are referring to. There is a protein osmotic pressure gradient going from Bowman's space to capillary (as the protein concentration is much higher in plasma than in the filtrate in Bowman's capsule. There is also a hydrostatic pressure in Bowman's capsule; this is simply the pressure of the fluid in Bowman's capsule.
Question: On page 6 you mentioned that the flux of a molecule can become saturated and reach a maximum.
Answer: Yes, this true of mediated transport.
Question: How does this occur?
Answer: If there are only X number of transport proteins for a given solute, and each transport cycle of that protein takes Y time, there is only so much of that solute that can be transported per unit time.
Question: And how is it separate from competitive transport?
Answer: Think about how that would relate now if that transport protein was not able to distinguish between several similar solutes.
Question: Can you descrive how myogenic control works? How does increaed pressure cause arterioles to contract?
Answer: Think about this as if you stretch these smooth muscle cells they contract more; as pressure goes up, that pushes out on these vessel walls, which is a stimulus for them to constrict.
Question: How does the macula densa sense the NA+ delivery to the distal tubule? Isn't the distal tubule located farther from the glomerulus after the ascending limb?
Answer: The macula densa is at the transition between the ascending limb and the distal tubule, where the tubule passes between the afferent and efferent arteriole. Don't worry about exactly how these cells of the macula densa sense Na+ flux through the macula densa; it is complicated and not fully understood.
Block 4 Immunology
No questions provided for this block.
Block 5 Gastrointestinal/Temp and Growth Regulation
Question: In type 1 diabetes, lactic acid secretion and ketogenesis can lead to metabolic acidosis, which can trigger hyperkalemia due to effects on renal transport mechanisms. I was wondering if you could clarify which renal transport mechanisms are being affected in type 1 diabetes.
Answer: The physiological reasons are complex, but this mainly has to do with the H+/K+ pump, which Dr. Sved mentioned is present in the kidney. Pumping H+ out in the kidney in exchange for K+ is a primary reason for the hyperkalemia.
Question: In your lecture notes for Gastrointestinal 1 you say that the small intestine digests fats slowly and so CCK is used to essentially buy time for the small intestine to deal with the fats present. However, you also say that CCK enhances peristalsis in the small intestine. Given that fats require time to be digested, I would have thought that CCK would impair peristalsis so as to once again give the small intestine more time to digest the fats. What am I missing?
Answer: Intestinal motility is usually very limited except for the migrating motor complex. CCK helps to start intestinal motility when fats enter the small intestine. It also lowers stomach motility. CCK with other hormones basically informs the intestine that materials are present, so motility needs to be initiated.
Question: Why is aspirin used to prolong pregnancies if aspirin will cause the ductus arteriosis to collapse? Would administering it before a certain period not have effects on the ductus arteriosis and still prolong pregnancy past the cut off for a viable fetus (approx 24 weeks)?
Answer: Aspirin is not used in the third trimester out of concerns of closure of ductus arteriosus.
Question: Would hyperthyroidism cause respiratory alkalosis?
Answer: It varies. Increased metabolic activity can result in metabolic acidosis. However, if vomiting is precipitated, the patient can suffer from metabolic alkalosis. Definitive changes in pH are not associated with thyroid disorders.
Question: In GI1, we learned that the distal part of the colon was innervated by the parasympathetic nervous system. So if our sacral spinal cord was damaged, how would this affect the colon? Would it lose all motility, or would it still have the enteric nervous system to help it?
Answer: Motility would still occur via the enteric nervous system, but the nervous system could not regulate the process. The changes in motility would be subtle.
Question: Is simply having lots of acid in the stomach sufficient to cause stomach ulcers or do you have to have your mucus layer weakened as well (either through H. pylori or alcohol/aspirin)?
Answer: Eating a high protein diet that causes substantial stomach acid production is usually not sufficient for ulcer production. The mucus layer has to be weakened.
Question: If Vitamin D is synthesized from cholesterol, do low cholesterol levels ever lead to Vitamin D deficiency, and by extension, hypocalcemia?
Answer: Low cholesterol levels would be associated with a host of disease symptoms, as the patient would have deficiencies in synthesizing all of the steroid hormones. Cholesterol is also present in cell membranes, and affects the movement of proteins in the membrane. Hypocalcemia would be one of a long list of problems.
Block 6 Reproductive and Developmental Physiology
Question: Is there any advantage Tamoxifen has over Raloxifene?
Answer: Tamoxifen is used more often to treat estrogen-stimulated breast cancer. I assume this is because it is a more potent antagonist of the estrogen receptor subtype in the breast than Raloxifene.
Question: I was reviewing material from the reproductive physiology lectures and had a question regarding Depo-Provera usage as a contraceptive for men. In lecture, you mentioned that the high dose of progesterone from Depo-Provera would result in no LH/no testosterone, and no FSH/sperm production. You then stated that this would still be an effective contraceptive even if testosterone were given back (I assume this would be to offset side effects such as decreased sex drive). Is this due to the fact that there would still be no FSH production? What factors are required for spermiogenesis? From my understanding, high levels of testosterone are required as well as growth factors produced via FSH.
Answer: Depo plus testosterone are an effective contraceptive regimen for two reasons:
- There would be no FSH production (as you state) and
- Intratesticular testosterone would be low. Normally, testosterone is produced in the Leydig cells, which are adjacent to the seminiferous tubules. Thus, the seminiferous tubules are exposed to an enormous amount of testosterone, much higher than the levels in the blood. Even when given testosterone, men on the contraceptive would have too low testosterone in the testes to support sperm development.