Block 1 Cardiovascular & Muscle
Question: I have a few questions from Monday’s lecture. You mentioned in class that if there is a slight increase in MAP, duration of isovolumetric contraction increases, leading to decreased stroke volume and increased ESV. I understand that in the following cycle, EDV also increases by the same amount that ESV increased by (entire curve shifts right). My questions are:
During this cycle, how much blood is expelled? If the curve shifted right by 10 mL does this mean that SV for this cycle is 10 mL higher than the first cycle? In other words, does the curve maintain this shifted position for every cycle (EDV always 145 mL and ESC always 75 mL)?
Answer: In general, you are correct. An increase in ESV usually leads to an increase in EDV and thus a more intense contraction in the next cycle. However, there are many nuances that we start to discuss today.
Question: If the SA Node is damaged, the AV Node-led HR hovers around 50. If B1 receptors are stimulated in that system, the effects are increased conduction velocity and contractility. Thus, is it true to say that there would NOT be an increase in HR in the system? Or, would the increase in conduction velocity (in the His-Purkinje system, specifically) also lead to a small increase in HR?
Answer:No—heart rate would likely be higher than 50 due to sympathetic nervous system influences. It would drive action potential generation in the AV node to be faster if the SA node is dysfunctional.
Note that conduction velocity and autorhythmicity in the system are different parameters. Autorhythmicity is the rate at which a cell produces action potentials spontaneously. Conduction velocity is the rate at which a cell transmits action potentials to the next cell..
Question: Last year, I shadowed in the UPMC Emergency Department and the attending explained to me that it is common for young patients' hearts (under the age of 25, I believe) to skip beats or have irregular rhythms. I do not remember the exact reason, but I believe that it had something to do with the intake of breath.
Answer:We will be covering this in an upcoming PBL. Breathing can affect cardiac output, which alters sympathetic and parasympathetic output to the heart via the baroreceptor reflex (yet to be discussed). This causes changes in heart rate, and can also induce arrhythmia.
Question: I have a question regarding alcohol and sympathetic output.
It's commonly reported that when drinking alcohol, people feel "warm" due to increased vasodilation on the skin surface. I concluded, then, that at some point in the signaling pathway, alcohol is acting to inhibit sympathetic output on B2 receptors. Further, I predicted that alcohol would likely be affecting output through modulation of pathways in the brain (and not the pre/post-ganglionic neurons).
I was at peace with this answer until I found a PubMed article "Effects of alcohol intake on blood pressure and sympathetic nerve activity in normotensive humans: a preliminary report." The abstract states "Our data suggest that acute oral administration of a moderate dose of alcohol induces a pressure effect through activation of sympathetic nervous outflow" (https://pubmed.ncbi.nlm.nih.gov/2632716/).
These two occurrences (increased BP and increased vasodilation), by the same source (sympathetic stimulation), seem at odds with each other. Is my conclusion regarding vasodilation incorrect? Or, would these two observations imply that alcohol is inhibiting one pathway (to B2 stimulation) while increasing another (to B1 stimulation leading to increased HR and BP)? Is it even possible for the body to to differentiate between the two pathways under normal circumstances?
Answer:You are on the right track in your thinking. Sympathetic outflow can be patterned, such than one group of efferents can have increased activity and other decreased activity. Sympathetic control of skin blood flow is distinct from control of sympathetic outflow to other vessels. It is definitely possible to vasodilate the skin and vasoconstrict elsewhere.
Question: I had a question about blood perfusion during exercise to the skin. It seems as though the skin arterioles would dilate so the body could cool off more effectively, but that would then take away blood from the skeletal muscle. What exactly is happening with sympathetic innervation to the skin during exercise?
Answer:Great question. The control of sympathetic outflow to skin blood vessels is almost entirely related to body temperature. The baroreceptor reflex has little impact on the firing of this cohort of sympathetic nerve fibers. This is the best example of patterning, or selective control of a small subset of sympathetic nervous system efferent fibers.
When body temperature is high, then the sympathetic outflow to skin arterioles decreases to permit vasodilation. Bradykinin release from sweat glands also causes local vasodilation in the skin, through a nitric oxide mediated mechanism.
Patterning of blood flow is one of my research interests in case you want to know more about the topic. The old dogma that the sympathetic nervous system is activated “all or nothing” is incorrect. Independent control of small subsets of sympathetic fibers in possible.
Block 2 Renal
Question: In class you mentioned angiotensin II increases Na+ reabsorption by enhancing Na+/bicarbonate transporters. Which regions of the nephron are these located?
Answer:The Na+-bicarbonate transporters are mainly in the proximal tubule.
Question: I understand that 67% of K+ is reabsorbed in the proximal tubule. What channels/transporters are used for this or is this mainly via paracellular transport?
Answer:You are correct—most K+ is absorbed through paracellular transport. The Na+-K+-ATPase causes sodium to move out of the proximal tubule cell and drives potassium into the cell. The extrusion of sodium creates an osmotic gradient and an electrochemical gradient. Water moves out of the PCT down the osmotic gradient created by sodium and Cl– moves down the electrochemical gradient. K+ is reabsorbed and follows Cl- into the bloodstream.
Note that plasma levels of Na+ and K+ are vastly different: a normal potassium level is between 3.7 to 5.2 mEq/L and a normal blood sodium level is between 135 to 145 mEq/L. Thus, more transporters and mechanisms are needed to reabsorb Na+ than K+.
Block 3 Respiratory & Hematology
Yet to come.
Block 4 GastrointestinalPhysiology & Metabolism
Yet to come.
Block 5 Reproductive Physiology
Yet to come.