Lecture notes for Friday, February 22
Embryology of the Heart
Remember that the heart develops from lateral plate mesoderm, by fusion of sheets of cells to form a single tubular structure. If a barrier is placed between these sheets, two hearts will form (analogous to the Driesch experiment).In contrast to the three different kidneys (pronephros, mesonephros, and metanephros) formed in embryonic development, you form one single heart (normally).
It begins as simple tube that contracts in a pulsating rhythm, and then becomes more and more complicated, dividing into four chambers, while beating and pumping blood the whole time!
Imagine re-building a lawn-mower motor into a 4-cycle car engine, while the motor is running full speed the whole time!
Before birth, blood does not need to be pumped through the lungs.
The following system for by-passing the lungs exists: until birth
There is a "trap door" opening between the right and left atria called the foramen ovale,
and also there is a short artery named the ductus arteriosus,
which connects the pulmonary artery to the aorta.
Without the ductus arteriosus, blood pumped out of the right ventricle would have no choice but to go to the lungs. Without the foramen ovale, only blood returning from the lungs would reach the left atrium.
Questions to think about and discuss in class:
a) Which direction does blood flow through the foramen ovale, prior to the moment of birth?
b) Which direction does blood flow through the ductus arteriosus before birth?
c) Why doesn't the blood flow in the other direction in the foramen ovale?
d) Why doesn't it flow in the other direction in the ductus arteriosus?
When the lungs expand and fill with air, that reduces the mechanical resistance to blood flowing through the capillaries: How should that change the relative pressures in left versus right atria?
e) What about the relative amounts of pressure in the aorta versus the pulmonary artery, before and after the lungs expand at birth.
f) The thickness and strength of the cardiac muscle walls of the right and left ventricles are the same before birth! But after birth, the muscles of the left wall gradually become about four-times thicker and stronger on the left side than the right side? What does that tell you?
Normally (in mammals) the tissues fuse together in both the ductus arteriosus and the foramen ovale, closing both permanently.
In as many as 25% of people, some small hole remains between the atria. (without any symptoms)
Many kinds of serious birth defects in human hearts result from improper formation of the interventricular septum (septal defects).
Sometimes the ventricles remain connected (not separated)
Sometimes the aorta or the pulmonary artery are connected to the WRONG ventricle!
Such "blue babies" can develop up to the time of birth, more or less "normally", but then have severe problems
Surgery can fix most of these problems; but it is one of the most difficult areas of surgery, I have been told.
OPTIONAL:
Last year Chris Cunningham, a medical student, was one of the teaching assistants, and he gave the lecture on heart development. You may want to look at these links:
Video links that were mentioned in the lecture:
classic animation used in medical school teaching
heart embryology animation using Claymation
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Circulatory System
The special kind of epithelial cells that line all blood vessels are called endothelial cells.The narrowest blood vessels are called capillaries, and their walls are made of endothelial cells only (one cell layer thick; and with few or no smooth muscle cells of fibroblasts to provide mechanical reinforcement or control constriction.
Arteries are made of layers of smooth muscle cells (and some fibroblasts) and type I collagen fibers wrapped around their capillary cells. We will talk about arteries, and especially their blockage by arteriosclerosis, in a later lecture.
Veins have fibroblasts and collagen wrapping the endothelial tube that lines where the blood cells are.
The first beginnings of the vertebrate circulatory system are a series of unconnected endothelial sacks, called blood islands, with red blood cells and white blood cells differentiating inside; most of these are in the yolk sac. Their endothelial cells crawl and connect to each other to form hollow tubes: the first capillaries. Only much later does bone marrow become the place where blood formation occurs; early embryos don't have bones; and when the skeleton does form it is nearly all made out of cartilage, which is solid, without a marrow, and isn't even penetrated by blood vessels (i.e. NOT vascularized) which is what you call it when these endothelial cells penetrate a tissue and form a system of capillaries, and later arteries & veins. Early embryos do not have any bone marrow yet, because nearly all their "bones" are still made of cartilage, and are solid inside. The yolk sac is one of several different organs that are used as locations for the hemopoietic stem cells which form red blood cells (and also white blood cells). These stem cells move to the liver, and later to the bone marrow.
Embryonic and fetal hemoglobins are different from (and coded for by different genes than) the hemoglobin we have in the red blood cells we make after birth. Fetal hemoglobin binds oxygen slightly more strongly than adult hemoglobin, which increases the amount of oxygen that is transferred across the placenta from the blood of a pregnant woman to the blood of the fetus developing inside her.
The genes for embryonic and fetal hemoglobin proteins are directly adjacent to the genes for adult hemoglobins, with the early blood cells activating one gene, and then later blood cells activating the gene next to that one. The mechanism isn't known, nor is it known whether there is any similarity to the mechanisms that cause adjacent Hox genes to be transcribed in adjacent tissues.
A few people continue to make fetal hemoglobin all their life, instead of switching to the adult hemoglobin genes, and the symptoms of this are almost unnoticeable! A new treatment for victims of sickle-cell anemia (and other genetic defects of adult hemoglobins), works by simulating hemopoietic stem cells back to transcribing the genes for fetal hemoglobin.
The geometry of the early vertebrate circulatory system is organized much like that of our distant fish ancestors, with blood being pumped front-ward out of the heart and around the sides of the neck in a series of 6 paired arteries like those used to provide blood to the 6 pairs of gills in a fish. Even birds and mammals form these aortic arches, even though there are no actual gills; they are in the places where gills would be. In mammals, the fourth left aortic arch becomes the aorta.
The vertebrate circulatory system begins as a series of unconnected endothelial sacks, called blood islands.
Most of these are in the yolk sac, in birds and mammals.
Maybe that's why mammal embryos continue to have yolk sacs?
Red blood cells and white blood cells differentiate inside;
Endothelial cells crawl and connect other to form hollow tubes: the first capillaries. Only much later does bone marrow become the place where blood formation occurs
Early embryos don't have bones; and when the skeleton does form it is nearly all made out of cartilage, which is solid, without a marrow, and isn't penetrated by blood vessels ("vascularized")
The yolk sac is one of several different organs that are used as locations for the hemopoietic stem cells which form red blood cells (and also white blood cells). These stem cells move to the liver, and later to the bone marrow.