Transposition of the Great Arteries

Aug 24 2009 Published by under Medicine, Science-y stuff

OK, it's time for another science-y post. Usually, I take on something very relevant to my specialty---it's a helluva lot easier to write about stuff I already know. But some basics are just really cool, and worth exploring, even though I'll have to step a bit outside my comfort zone. In this case, it's the heart.  Because I'm venturing a bit on the wild side, I consulted an expert, whose hot, hot science helped illuminate this topic.

If you've taken a basic biology course, you probably have some idea of how the human heart works, but understanding can be a bit deeper if we look at the heart through the lens of things that can go wrong.

The heart is one the most easily recognized and, yet, mysterious organs in the human body.  Physicians of the Hippocratean school first described the valves of the heart in the 4th century B.C.  Since, the heart has historically been described as the core of love,spirituality, intellect, and emotion.  The heart was originally thought to be the source of conscious thought.  The heart is a recognizable icon, source of stress for some of us who have witnessed friends and family with cardiovascualr disease, and a subject of poetry and song.  However, to the physician and physiologist, the human heart is simply a pump whose primary purpose is the circulation of blood throughout the circulatory system.  In fact, the majority of cardiac physiology and pathology (disease) can be easily demystified and understood by thinking of the heart as a mechanical pump.


Human heart, post-mortem obviously

The heart is a pump

The heart has one basic function -- to receive oxygen poor blood from the body, pump it to the lungs where it can be replenished with oxygen, and then pump it back to the body where that oxygen is needed.  

If we sliced through the human heart we would find that it has four compartments or chambers.  The top chambers, or atria (singular = atrium), receive the blood.  The lower chambers, or ventricles, pump the blood.


Human heart from Gray's Anatomy showing the four chambered heart.

The following diagram illustrates how blood travels through the heart:

blood path.gif


 Image courtesy Isis the Scientist

  1. Oxygen poor blood returns from the body and enters the right atrium
  2. Oxygen poor blood passes from the right atrium to the right ventricle.  The right ventricle then pumps the oxygen poor blood into the pulmonary artery.   Sometimes people are confused by the pulmonary artery because most people think of arteries as having oxygen rich blood.  The true definition of "artery" is any vessel that takes blood away from the heart.
  3. Oxygen poor blood from the pulmonary artery travels to the lungs where the oxygen is replenished.
  4. Oxygen rich blood returns from the lungs and enters the left atrium
  5. Oxygen rich blood passes from the left atrium into the left ventricle.  The left ventricle then pumps oxygen rich blood into the aorta.
  6. Oxygen rich blood from the aorta is then circulated through out the body.  The oxygen is utilized and the blood becomes oxygen poor.  Return to step 1 and begin the cycle again. 

As you may see, the heart and lung essentially function as a single "super-organ" whose purpose is to gather blood, oxygenate it, and return it to the body.  Here's a schematic of the process we just described, for those of you who like simpler diagrams.


This schematic simplifies what this dual-organ does. Oxygen rich blood is pumped from the left side of the heart to be used in the body. "Used" oxygen-poor blood returns to the right side of the heart where it is pumped to the lungs for a refill. The newly-oxygenated blood returns to the left heart to continue the cycle.

To understand just how important this rather basic plumbing is, let's look at what happens when something goes wrong.

Transposition of the Great Arteries

During development of the fetus, bad things can happen to the heart-lung's plumbing. There are many kinds of congenital heart defects, but one which will serve as a reasonably useful example is called "transposition of the great arteries" (TGA). 

Before birth, blood is shunted away from the lungs, mostly via a connection called the ductus arteriosus (DA, #3 in the sketch below), since breathing amniotic fluid is not particularly useful.  The DA connects the aorta and the pulmonary artery, allowing blood to bypass the lungs.  As soon as a baby is born, a set of physiologic changes occurs which closes the DA.  Once the DA closes, blood flows normally, entering the right heart, being pumped to the lungs by the pulmonary artery, and back to the left heart, thence to the rest of the body again.

In TGA, this normal post-natal flow is altered.  The "great arteries" of TGA are the aorta and the pulmonary artery (PA). Below is pictured an anatomical schematic, and a stripped-down version.  The aorta is the red one that carries O2 rich blood to the body. The PA is the blue one that carries O2 poor blood to the lungs. In TGA, these two get switched during development, with the PA pumping blood to the body instead of the lungs, and the aorta pumping blood to the lungs instead of the rest of the body.  Since the fetus doesn't rely on the lungs, there aren't any problems until birth, when the fetal circulation is switches to a normal post-natal one.



Schematic of TGA

You can see that rather than having the normal serial circulation, in TGA there is a parallel circulation in which blood supplying the body fails to get oxygenated. Oxygen rich blood from the lungs, rather than being pumped into the systemic circulation is pumped back to the lungs in an endless loop.  Over on the right side of the heart, oxygen-poor blood from the body simply recirculates without ever making it to the oxygen-rich environment of the lungs.  This is a problem. Most babies born with this problem are quite ill, and their blue hue signals a "cyanotic heart defect".  Most will die quickly without immediate intervention.

It's often impossible to do a definitive operation immediately, so there are procedures that can temporarily save a baby's life.  Once such clever intervention is known as the Senning Procedure.  In this procedure, a catheter is snaked from a blood vessel in the thigh up into the heart and a hole is created between the atria.  This hole (called an atrial septal defect, which can also occur naturally) allows blood from the oxygen-rich left heart to mix with blood from the oxygen-poor right heart, and thence circulate to the rest of the body.  Another common intervention is infusion of a medication to keep the ductus arteriosus open, helping to keep oxygenated and deoxygenated blood mixing.  These two interventions can save the baby's life until open heart surgery, where the two arteries will be switched back into their proper positions.  

Heart-lung physiology is pretty cool stuff, and there are lots of online resources from basic to complex, so go and learn.

26 responses so far

  • Nice work, Pal. Now you're an expert too!

  • Russell says:

    Is TGA usually accompanied by other, lesser abnormalities in heart physiology? It seems a bit strange, developmentally, to have such a "clean" swap in plumbing. Is much known about the developmental path that causes it?
    A related question: how deterministic is the topology of veins and arteries? For example, are the pulmonary arteries always dorsal to the superior vena cava? Or can they ever be ventral to it? And if that happens, is it a serious defect? Or just someone who has weird anatomy? (In the last figure, I assume 3 labels the ductus arteriosus.)

  • Ramel says:

    Nice post Pal, it's always cool to see this stuff presented in a way we non-medical types can understand.

  • PalMD says:

    Russell, the answer to all of your Qs is basically "yes". There are several different types of TGA, many with associated abnormalities, but the embryology of the heart does allow for "a clean swap" of sorts. The type of TGA described here "simple" rather than "complex", meaning associated with other defects. If you want to see crazy, read up on Tetrology of Fallot.

  • Mu says:

    It's amazing what they can do, both diagnostic and early-intervention, on TGA nowadays. I lost a newborn brother to a TGA-type condition in the 70's, and I remember till today how frustrated my father was when he found an article describing the first open-heart surgery for the condition on a newborn not six months later. Sometimes I feel we're losing the perspective on what all was killing folks 20, 50, 100 years ago, and how easy we have it nowadays. Probably losing the gratitude to those who make the progress too.

    • michael says:

      Hi there.
      I have had 2 boys born with TGA and a girl who is perfectly fine.
      Both boys were only diagnosed after birth. Even after doing a scan on the second boys heart.
      My first born died 5 years ago at only 3 days old after an 11 hour arterial switch operation. Complications with the coronary arteries caused him to pass away in theatre. Then my girl was born 3 and a half years ago. We had a featal heart scan done and she was fine. 7 weeks ago we had another boy. He also had a featal scan done and they said the heart was fine. He passed away last week.
      the arterial switch went off perfectly and his heart was working 100%. He then picked up infections in the ICU due to being in there so long. He also had N.E.C. A stomach condition some prem babies get.

      Does anyone know of one family having this happen to them twice???
      And are there ways to test and see if this is genetic? we would love another child but would not know how to cope if this had to happen again.

      • DT35 says:

        I am not medically trained but I just finished the book "Walk on Water," an account of pediatric heart surgeons who practiced at the Cleveland Clinic about 12 years ago. IIRC, the head surgeon told one family that there was about a 1% chance of some cardiac defect in any pregnancy, and a 3% chance if the couple had already had a child with a heart defect. Whether these same figures apply to TGA specifically, or whether they are still felt to be valid so many years later, I have no idea.

        It seems as if your son's heart surgeon or your wife's OB/maternal-fetal medicine specialist should be able to give you some idea of the risk in your particular situation, or could refer you to a geneticist for a knowledgeable assessment.

        Best wishes to your family.

  • Steve says:

    Great Article! As an adult living with a heart defect (Tricuspid Atresia) it is always good to see a serious, complex defect explained so simply. Thank you!
    Adventures of a Funky Heart! blog

  • dan says:

    my son will be subjected to an arterial switch this week. he has d-transposition with septum defect. do you know children who already got well after this?

  • (In the last figure, I assume 3 labels the ductus arteriosus.)

    If'n I were a betting woman, I would say #1 is the foramen ovale, #2 is the aorta, #3 is the ductus arteriosus, and #4 is the pulmonary artery.

  • daedalus2u says:

    What regulates the detailed anatomy of the vasculature is not well understood. I think that a great deal of it is regulated by gradients in NO, with hemoglobin being the sink for NO. I suspect that hemoglobin being a sink for NO is what sets the capillary spacing.
    It can't be gradients in O2, because the vasculature is still well formed even when there aren't large gradients in O2 (such as in utero and at rest). The pumping of blood in vessels occurs long before the placenta has the capacity to supply O2 (which can’t be supplied until there is a well-vascularized placenta).
    Most differentiation, organogenesis and even neurulation happens in the first trimester when O2 levels are ~ 20 Torr, before the rise in O2 levels that happens at about 12 weeks.
    I think it is better for the vasculature to use gradients in NO (with vessels being the low NO site with oxyhemoglobin being the sink for NO) instead of O2, because significant gradients of O2 are needed to supply O2 at a high flux. Those gradients necessarily are greater outside the vasculature, and are quite variable at the vessel wall and are quite small at rest (when most vascular remodeling occurs). A fetus is always “at rest”, so vascular spacing can only be determined “at rest”.
    I think that low basal NO then explains the capillary rarefaction of conditions such as systemic sclerosis and Raynaud’s. With Raynaud’s that results in a control instability, when there is a slight constriction (as from cold perhaps), there is insufficient O2 which causes mitochondria to generate superoxide which pulls the NO level down, causing vasoconstriction, more O2 depletion and positive feedback from more superoxide. When the O2 level gets low enough, and the superoxide producing capacity is exhausted, the NO is made from the reduction of nitrite which then reopens the vasculature. That NO also blocks the heme enzymes reducing the superoxide formation on reperfusion. If you raise the basal NO level, the capillary rarefaction doesn’t happen.

  • DebinOz says:

    I've just sent this off to my daughter who is studying physiology at university.

  • Christina says:

    Thanks for the easy to understand explanation. My son was born with TGA and has his switch operation when he was 5 days old. He is now 2 years old and is doing well.

  • 50 mmHg, daedalus? In the human umbilical artery? That's higher than PO2 in the extrautero venous circulation. I hate to call "bullshit" on my one true daeudalus, but they measured PO2 in the placenta, not in the umbilical artery. I'm not so sure that PO2 in the fetus changes as drastically as it does in the placenta...
    Check out this hotness that includes some work where the umbilical artery of animals was cathertized..:
    Meschia, G., Placental Respiratory Gas Exchange and Fetal Oxygenation. 5th ed. Maternal-fetal medicine : principles and practice,, ed. R. Creasy, Resnik, R, Iams, JD. 2003, Philadelphia: W.B. Saunders Co.

  • daedalus2u says:

    My dearest Isis, you need to do a material balance like an engineer. The fetus only gets O2 from the placenta. The fetus consumes O2. O2 only diffuses passively in mammals (there are a few organisms that actively transport O2 and can reach 100 atm partial pressure O2, but not mammals). The partial pressure of O2 in the fetus is less than the partial pressure in the placenta. It has to be.
    I found the book you mention online, and they have data that is completely consistent with the paper I cited. Uterine artery 72, uterine vein 42, umbilical artery 19, umbilical vein 28 mmHg O2. table 15.2
    Look at figure 3 in the paper I cited. They measured uterine and placental O2 levels and in every case the uterine level was higher than the placental level.
    Look at figure 6. The nitrotyrosine staining is low at 6 weeks, high at 9 weeks and low again at 13 weeks. The nitrotyrosine is a marker for the transition from a state dominated by NO to one dominated by O2.
    My point was how the O2 levels are changing over time. The vasculature is well formed in the fetus during this entire period. If O2 is somehow regulating vasculature development and spacing it can only be the O2 partial pressure that is the control parameter (the control parameter must be an intensive property like partial pressure, not an extensive property like O2 content (which is highly nonlinear because hemoglobin has a nonlinear O2 affinity)). If O2 partial pressure is varying by a large factor, how can it be the control parameter for vessel spacing? Because the tissues are consuming O2, the O2 levels between the vessels are even lower. Capillary spacing can’t be regulated by O2 levels.
    I understand that vascular physiologists tend to use parameters such as “oxygen extraction” which are completely non-physiological and useless for understanding what is actually going on. O2 only diffuses passively down a chemical potential gradient. Hemoglobin carries O2, but the partial pressure in red blood cells is identical to that of the plasma they are floating in.

  • daedalus, did they measure PO2 in the fetus? And how does this article support your hypothesis about "oxidative stress" regulating development of the vasculature?

  • Most differentiation, organogenesis and even neurulation happens in the first trimester when O2 levels are ~ 20 Torr, before the rise in O2 levels that happens at about 12 weeks.

    Wait, wait, wait! I missed this one the first time. The truncus arteriosus grows and divides into the aorta and pulmonary artery between weeks 4 and 5 of fetal life. The heart is four chambered and fully functional by week 8...long before your PO2 changes at week 12.
    daedalus, I love your NO hypotheses, but I do not believe they are a major cause of great vessel abnormalities.

  • daedalus2u says:

    Dearest Isis, I don't think that perturbations in basal NO are a major cause of great vessel abnormalities either. I don't think that "oxidative stress" or even O2 levels is a major factor in regulating the development of the vasculature, other than how it affects NO.
    That was my whole point. The vasculature in a fetus is "well developed" from conception to birth. Much of the early metabolism is supported by glycolysis, while the O2 levels change quite dramatically and are always considerably lower that the O2 levels in the vasculature in all humans after being born and breathing air. O2 is not a suitable parameter with which physiology can regulate vascular development, particularly capillary spacing which is a critical parameter.
    The problem of capillary rarefaction (observed in hypertension, systemic sclerosis, Raynaud’s and peripheral vasculopathy) is due to low NO and the normal capillary spacing physiology working correctly, not perturbations in O2 or oxidative stress (other than how oxidative stress affects NO).

  • daedalus, I am now completely confused.

  • daedalus2u says:

    In my first comment when I said "the detailed anatomy of the vasculature", what I was thinking about and meaning was the smallest details, the location and spacing of capillaries and the next larger sized vessels.
    Capillaries have to be well formed and spaced accurately throughout the entire lifespan. That is regulated continuously and is part of the continuous remodeling of the vasculature that is always going on.
    That spacing is messed up in diseases associated with peripheral vascular damage. The disruption is ongoing, so it must be a setpoint issue. The disruption is widespread, so it must be a systemic issue. The disruption is observed in many different diseases. That disruption is made worse by stress, diabetes, hypoxia, and other things. Everything that seems to lower NO makes it worse, everything that seems to raise NO makes it better. Presumably there is a final common pathway that leads to that disruption, but that the different diseases achieve that final common pathway from different directions.
    I think that final common pathway is low NO.

  • nash says:

    are there any cases that tga might have no cure and is impossible for a surgery except for health status of the patient?

  • nash says:

    im studying for it.. we are having a grand case to weeks from now.. need your reply pls.. thanks

  • PalMD says:

    I'm not PubMed.

  • Hannah says:

    I am 22 years old and had the sinning procedure when i was 5n weeks old.
    I guess everything went well seeing as how I am 22 and still living.
    It would be nice to know what caused the abnormality in my heart. I don't understand anything in the already mentioned comments above, I am not medically educated other than what I have learned via the doctors office....
    But how neat it is that you've put all this in more simplistic terms.

  • PalMD says:

    That comment made the whole bit of work more than worth the time and effort.