Cardiology Confusion I

It's been a long week. We're back in tutor group, which is Cornell's problem based learning format. I came to Cornell in large part for the problem based learning aspect of the curriculum, and as I anticipated, it definitely beats sitting in lecture all day. That said, it can be pretty exhausting. I forgot just how much work it can be since last being in tutor group in the fall.

What can make problem based learning so time consuming is that it is often very open-ended. My group made a big effort to make our "learning issues" very specific, but I still ended up researching subjects as enormous as "the progression of heart disease." In fact, I spent Wednesday afternoon, evening and part of the night as well as Thursday evening trying to teach myself everything there is to know about the progression of heart disease. In retrospect, this was a completely ridiculous expectation on my part as their are whole books written on the subject, and some important species variations/predisposing factors, but at the time it somehow seemed entirely reasonable to me. And to my credit, I did a good job of covering a whole heck of a lot of ground those twelve hours in the library.

So for those of you who are interested, here is an abbreviated chronicle of my discoveries.

First off, I approached the problem of the progression of heart disease with the wrong paradigm in mind. I assumed initially that it had to be anatomical changes, such as degenerating mitral valves, that were driving the disease progression. This is true sometimes. But what is more true is the principle that compensatory mechanisms that work in acute situations actually cause the progression of heart disease when they are chronically activated. This finally sunk in after reading that, "Clinical signs observed in heart failure are mainly the result of chronic activation of compensatory mechanisms to restore and maintain blood pressure." And, "A common characteristic of all compensatory responses is that the short term effects are helpful but the long-term effects are deleterious."

With my new perspective, I tackled the compensatory mechanisms that are triggered by heart disease rather than looking for anatomical changes leading to heart failure (however, the two are not totally unrelated). This was after reading a great deal about myxomatous degeneration, genetic factors leading to valvular degeneration, and other factors promoting degeneration of valves such as the loss of the endothelium.

I identified three separate compensatory pathways that result from low blood pressure and volume or pressure overload: activation of the sympathetic nervous system, activation of the renin-angiotensin-aldosterone-system and hypertrophy (eccentric or concentric) and followed each pathway until it led to decompensation (i.e. ultimately feeding back on low blood pressure and creating a vicious cycle).

Then I went and read about drugs that are commonly used to treat heart disease/failure-- their mechanisms and how they alter the compensatory pathways and progression of the disease.

I got really hung up on two points. First, I couldn't understand how mitral valve regurgitation (which is very common in older dogs and was part of the presenting problem in our case) led to low stroke volume. The equation for stroke volume is:
stroke volume= prelooad + contractility -afterload. Well, none of these were changed by the mitral valve regurgitation and so I went in circles trying to understand how the stroke volume was reduced. It turns out to be a special case-- stroke volume is decreased because a portion of the blood is flowing backwards into the left atrium, not due to the other parameters at all! Sometimes it pays to think outside the box a little bit.

I also got stuck on the subject of volume overload. I knew that there had to be volume overload because of the eccentric hypertrophy (which is triggered by volume overload and increased diastolic wall stress in simple terms, though as I discovered after consulting several sources, no one really knows exactly how these factors trigger hypertrophy/what the exact mechanisms are). The key to thinking about the cardiovascular system is that it is a CLOSED system. What the heart pumps out returns to the heart (except in special cases such as hemorrhage). So how does mitral valve regurgitation cause volume overload? I kept thinking that if more blood is showing up in the left ventricle, then it must somehow be lost from another part of the system, but where??? Of course, this doesn't makes much sense. What a kind and brilliant professor finally explained to me is that the volume overload is a result of the low blood pressure (that comes from the low cardiac output that comes from low stroke volume that comes from a significant portion of the blood flowing back into the left atrium instead of the aorta). As a result of the low blood pressure, glomerular filtration rate is reduced, and so less fluid leaves the system, leading to volume overload.

And then there is the whole subject of the renin-angiotensin-aldosterone system that kicks in to help raise blood pressure. But doesn't help long term. I spent quite awhile pondering this as well. From my beloved Boron and Boulpaep (yes, I'm having an affair with my physiology textbook): "Common to these edematous diseases is an abnormal shift of extracellular fluid away from the effective circulating volume... The reason that most of this added extracellular volume remains ineffective and does not restore the circulating volume is not intuitive but reflects the underlying disorder that initiated the edema in the first place. Thus treating these diseases requires generating a negative Na+ balance."

If you made it to the end of this post, you deserve an award. I'm so tired that I am going to bed shortly. Trying to learn the physiology of the cardiovascular system in one week was way too much work but I think I've got the core concepts finally:)