YEASTING 11/17/2009 Review and some Objectives by Ernest
Review:
Development of diaphragm:
Let’s review a little bit. If we look at the developing embryo in the area that is going to become the diaphragm we have tissue from septum transversum. That’s anterior/ventrally situated just caudal to the heart after the folding process has occurred. We see the primitive furrow cavities, the caudal end of the primitive furrow cavity, or the pericardial or peritoneal canals. These canals have pinched off from the pericardial space more cranially. They will pinch off from the peritoneal space caudally here at the level of the developing diaphragm as the pleural peritoneal folds develop. These pleural peritoneal folds develop in the posterior aspect of the pericardial peritoneal canals at the level septum transversum. Those folds will increase in size and grow into the canals and ultimately meet with the tissue derived from septum transversum.
Also coming off the posterior body wall meeting with septum transversum during the folding process is mesentery related to supporting structures, the gut, and most specifically the portion of gut that’s found at this level of the caudal esophagus. So the meso structures, the supporting structure that support the esophagus, take blood vessels to it have nerve going to it etc. will be the mesoesophagus or here its called the esophageal mesentery. So now we see that we have septum transversum, the mesoesophagus, and the pleural peritoneal membrane helping to form the diaphragm.
At the same time this is happening, we talked about around the heart the pleural cavities, pericardial peritoneal canals that are initially posterior next to the esophagus on either side of the esophagus dissect anteriorly in between what will become body wall and what becomes tissue around the heart, the fibrous pericardium. That dissection not only occurs from posterior to anterior by these primitive pleural cavities but also extends from superior to inferior. So basically we start out with a relatively flat primitive diaphragm here and then with excavation of body tissue inferiorly along what will become the margin of the diaphragm, excavate the central region of the diaphragm away from the body wall, and thus instead of having a flat diaphragm the diaphragm becomes domed shaped. The areas here to the side of the domes between the diaphragm and thoracic wall are caused by the dissection of the pleural spaces down inferiorly. So connective tissue is being taken away from body wall or sliced off the inner aspect of the body wall and given to the periphery of the diaphragm. So that’s what we see here, we’re looking from the peritoneal or abdominal aspect. We would see the similar structure if we were looking from the dorsal aspect but those portions that have been dissected away from the body wall would not be as evident because they would be in a recess/depression.
So here we see schematically at least the central tendon of the diaphragm formed from septum transversum we see a large area here that is said to be ingrowth from body wall muscular in growth from body wall. I would cross out the muscular. Connective tissue yes but muscles are not growing in from the body wall at this level and we’ll come back to that.
Here in the posterior midline coming up into the central region we have the mesoesophagus and structures that it contains, and we see little areas to the side that are remnants of the pleural peritoneal folds or membranes. Now the reason I take exception to this statement here “muscular in growth from body wall” is that:
Where do the muscles muscle fibers that inhabit the connective tissue of the diaphragm come from? When do they come into the connective tissue that we know of as septum transversum? What’s the innervation of the diaphragm?
“Cervical 3,4,5 keep the diaphragm alive.” Okay usually you can tell where a muscle mass came from by tracing its nerve supply. So if the nerves coming into the diaphragm to provide motor and sensory innervation to it, especially the central portion of it, are from C3,4,5 where do the myoblast come from? These are the myoblasts that grew into septum transversum connective tissue and then continued on as they proliferated into the connective tissue that were added from the body wall into the connective tissue derived from the mesoesophagus.
Where do those original myoblast come from if the nerve supply is from cervical 3,4,5? Spinal nerves. Somites. Cervical 3, 4, 5. When the folding process takes place and they kind of stretch the anterior aspect or cranial aspect of the embryonic disc and mold it around what becomes are part of the gut, if you will, the foregut becomes pharynx esophagus. Septum transversum that was the leading edge of the disc ends up in the cervical region of the embryo. There muscles fibers, myoblasts, migrate in and populate the connective tissue nerve fibers and follow along and then with differential growth the diaphragm relatively descends down into the area we know of it at the caudal thoracic level. So when we say septum transversum makes the central tendon pleural peritoneal membranes here, the tissue here, the tissue here, really we’re talking about connective tissue population sources that are then populated by the muscles.
So the muscles muscle fibers of the diaphragm motor wise are going to innervated from cervical spinal nerves 3 4 5 by the left and right phrenic nerves. The central area of the diaphragm, the top of the dome if you will, and coming down away on the side of the dome sensory wise is also innervated from C 3, 4, 5 levels.
But the portion where we’re getting down to the diaphragm attaches to the ribs the connective tissue there was separated away from the body wall and took with it branches of intercostals nerves that are in the area. So the periphery of the diaphragm, the edge of the diaphragm, is innervated by intercostals nerves that are in the area. The center area of the diaphragm sensory wise is phrenic nerve and all the muscles that inhabit the diaphragm are also phrenic nerve C 3, 4, 5.
Now a very real example was my mother in her last months was having pleural fusions. She didn’t know about this but she said my shoulder hurts. Dermatome 3, 4 here. So the fusion was enough that it was irritating the pleura on the dome of the diaphragm just lateral to the heart and she was getting referred pain and it felt like sensation was coming from the shoulder. She also said it feels like I have a band around me. That was due to the irritation of the top of the diaphragm, the pleural aspect of the diaphragm here at the periphery where the sensory innervation goes into inner costal nerves. Here we’re looking down from the thoracic aspect we see a central tendon area connective tissue in the middle diaphragm and then all the way around radially running muscle fibers. The central tendon is of septum transversum origin. The periphery out here is that it was scraped off the inner body wall. Here’s what I was talking about the diaphragm being dome shaped, the center area is the septum transversum origin, the side of the dome is tissue that was separated away from the tissue becomes the thoracic wall. This portion here is innervated sensory wise by innercostal nerve branches, this area is innervated sensory wise by phrenic nerve, all the muscles that inhabit the connective tissues are innervated motor wise by phrenic nerve.
Pleural Peritoneal Membrane and Bochdalec Hernia:
Now things can go wrong. One of the more common defects within the abdominal thoracic region is that the pleural peritoneal membrane doesn’t develop or fuse. Thereby we’ll have a hole in between the abdominal cavity peritoneal cavity within the abdominal cavity and the pleural cavity. As the intestinal tract and other abdominal organs grow they create pressure within the abdominal cavity. A point of release of that pressure is through the defect so we’ll find coming up into the (usually) left pleural cavity intestinal tract. Intestinal tract within the pleural cavity then pushes the left lung down so it cannot expand properly grow properly often times pushes the heart over to the right and compromises the right lung development. In some cases, the membrane may form but not have muscles grow into it so that membranes remain weak and instead of having a frank opening that the intestinal loops will pass they push the weak tissue ahead of it so that we actually have a hernia sac extending from peritoneal cavity up into the pleural cavity. Still damage is done to the lungs, heart still moved, but the intestinal tract is not technically within the pleural cavity itself. Its within a recess of weak tissue of the diaphragm.
What do you think is going to happen if the pleural peritoneal membrane does not form on the right side?
Liver’s a pretty good-sized organ so the hole tends not to be as big if it forms on the right side.
What do you think the liver is like as an organ? Any ideas? Its semi-soft its plastic its malleable so you can see often times in those individuals that do have a right posterior lateral diaphragmatic hernia you can see a little knob of liver pushing up into the pleural cavity but its most devastating if the posterior lateral defect is on the left side. Because the livers not there to block migration of intestinal loops it would come up into the pleural cavity. So here we see an individual with a posterior lateral defect its called Bochdalec hernia. The intestine passes through and severally compromises the left lung development. The right lung development is also affected so the little ones who are born with this are in severe difficulty.
One of the first fetal surgeries that was carried out was where the fetus was delivered temporarily out of the uterus, the umbilical cord was kept connected to placenta, repair of a Bochdalec hernia opened the little one put a mesh in and basically closed the foramen after they pushed the intestinal loops down in the abdomen, put the little one back in, and sowed up the uterus, crossed there finger, the little one survived and is still living.
Right vs. Left foramens:
So both of these foramen where the pleural peritoneal membrane are in the posterior lateral aspect of the diaphragm the right one tends to close earlier than the left, the right one tends to be protected by the liver so if the right one doesn’t close the liver closes the hole the liver may push up since it partially plastic pushes up a little bit into the pleural cavity. The ones that are devastating are on the left side tend to be large. Intestine, spleen, etc. can migrate up the pleural cavity and thereby compromise severely lung development. The problem with the little is not that they have a hernia when they’re born, it’s that their lungs are not developed.
Objective 1: Briefly explain why the conceptus is not immunologically rejected by the mother during and following the process of implantation.
Reason 1: Syncytiotrophoblast doesn’t have much surface antigen
Reason 2: The T-Helper cells and Natural Killer (NK) cells are suppressed by the decidua reaction. This is important because cytotrophoblast has antigenic markers. Cytotrophoblast is usually deep to syncytiotrophoblast but through the anchoring villi the cytotrophoblast grows and comes to the outside of the syncytiotrophoblast-deciduas interface and spreads laterally. Even with the syncytiotrophoblast capping around the ends of the broken blood vessels that have penetrated in by the syncytiotrophoblast. Now cytotrophoblast cells that are elaborating surface antigens are exposed to maternal tissue. And would excite an immune response if the lymphocytes in the area were not down regulated.
What two major populations of lymphocytes does the maternal body have? As for location?
We have lymphocytes within the tissues and within the extracellular space this is where they do their work so there will be the lymphocytes in the endometrial stroma the ones that are found in the deciduas, the altered endometrium, exposed to the prostaglandin etc. being released and synthesized by the deciduas cell
Might there be any other major population of maternal lymphocytes? Those that are circulating.
What would the circulating lymphocytes come in contact with? With syncytiotrophoblast. And we’ve already said that syncytiotrophoblast has not elaborated many surface antigens also things: fibrin and other chemicals within the blood tend to be deposited on the surface of the syncytiotrophoblast and will hide any antigens that are there. Those are the major reason that the conceptus is not rejected.
What’s the genome like in the placenta syncytiotrophoblast and cytotrophoblast in comparison to the embryo fetus? What’s the genetic complement like in the supporting tissue as compared to the embryo fetus?
It’s the same. Hence if you want to sample the genome you can either take amniotic fluid that has cast off cells from the surface of the embryo fetus, spin that down, analyze the DNA within those cells or you can sample the placenta. Now it just so happens that the male portion of the genome tends to be expressed more in the placenta in the supporting tissues then it is within the embryo fetus. The female portion of the genome the maternal portion of the genome tends to be expressed more heavily in the embryo fetus. So the father, paternal aspect, is already supporting playing a major in the support of the embryo fetus even before birth. I kind of remember that in the sense that you maybe still supported by parents I supported three through so father supports the little one before birth and after birth for many years.