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This on-demand teaching session will discuss the embryology of upper and lower limb structures, from the formation of the zygote to the formation of bones and cartilages. It will explore the various theories of limb development in terms of how cells differentiate and migrate in order to form various structures, and how hormones/enzymes and genes could affect the growth and shape of the limb. Through examining various conditions, the session will also cover definitions of malformations, deformations and dysplasia, classification of certain upper limb conditions, healing of fractures, and how intramembranous and endochondral ossification works. This session is pertinent to medical professionals and is essential for those preparing for the FRCS exam.
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Learning objectives

Learning Objectives For This Session: 1. Describe the embryological process that occurs during upper limb growth. 2. Explain the influences of FGF, Sonic HedgeGog, and WNT/ NGrade 1 on limb development. 3. Distinguish between Malformations and Deformations of upper limb development. 4. Define Intramembranous and Endochondral Bone formation. 5. Understand the role of the Ectodermal ridge, Zone of Polarization, and Pike Electrodermal Ridge in upper limb formation.
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Computer generated transcript

The following transcript was generated automatically from the content and has not been checked or corrected manually.

Um So, apologies, it's like a deconstructed apple pie. You had the pie. Now, unfortunately, you need to cook the apple. Um So, apologies for this site mix up in the order. Um So we're going to talk about embryology, mainly upper limb embryology. Um The I would assume it's the same for the lower limb as well, but it'll be enough for you. Uh You know, this is what you need to know for the exam as well and we're gonna talk about normal growth, you know how the limbo develops, you know, what are the different parts and what really happens. And then we talk about, you know, some classic deaf uh definitions for, you know, deformation, dysplasia, malformations. And then just very briefly, I'm just going to touch on some classifications for upper limb uh conditions. Uh all of which you've, you've gone through in, in the proceeding talk. So this is just going to be a slight whistlestop tour. I'm not, I'm just going to bring you back to the, you know, unicellular stages. So you have the egg which gets fertilized to form the zygote and then you have, you know, two cells, four cells and then you have a multicellular uh embryo and then, you know, from the uh the moral of the multi cellular structure, you start getting some form of organization there. And as you can see, uh that organization continues to this area, which is the inner cell mass, which then forms the by laminar germ disk where you only have the ectoderm and the endoderm. Uh and then the endoderm will differentiate and invaginated uh in here forming the mesoderm. And so then you have the three layers, the ectoderm, endoderm, sorry, ectoderm, mesoderm and endoderm. Um And just so that you're so and that forms the try laminar germ disk. And then when you section that these are the classic pictures that you see in your embryology. So this is now uh still at three weeks, you have uh further differentiation. Uh And then you have uh version of the endoderm forming the notochord uh as you can see here. And I'm not going to go into too much detail, we will touch on this but the mesoderm condenses around the uh the, the notochord uh and the ectoderm to form uh So mites which, which we will discuss uh you know, forms different MS dermal structures. Um And this is what this structure as you can see in longitudinal looks like. Uh And then you have the, the central canal that forms on the inside and then these are the condensations or the. So mix around that you don't need to know this in, in a lot of detail, but it's just important, you know, before you start drawing the limb buds uh to understand where this structure comes from. Okay. So what do we know what structures come from? The Ectoderm? Commonly any guesses some of it is is there? So you have the neural crest, neural tube forming all the nervous tissue and then you also have the typical ectodermal ridge, which is a which is overlying the mesoderm allows condensation there. Okay at the start at the start of the limb. But do you know what structures come from the mesoderm? Is it more the muscles and bone? Yeah. So, so as you can see here from so might, you know, you have somatic tissue uh and and that forms your muscular structures, you know vascular structures and then from the lateral plate, you have the bone bony structures for me. Okay. And then we know that all our visceral organs come from the endoderm. Okay. Um So this, you know this structure over here, which is your early foetus, then you know undergoes folding and you have uh you know cranial Kordell differentiation and all this is happening under the influence of various enzymes which we will go through. So the important bits that we're going to focus on are the the lateral museo dermal plate. The so might uh and the formation of the limb, but that occurs around four weeks and this is really where your F R C S answer starts from. So there are three theories of limb development. So first thing is we, we truly don't, you know, have a full handle. We know of some important aspects of limb development, but we really don't understand the exact theory. So one theory suggests that uh cells proliferate and they push forward, they pushed the growth ahead, led by the epical ectodermal ridge, which is this red area at the top. And that tells the limb where to go and what to form. And the cells then follow the direction. There is an early specification model which says that the cells are actually predetermined. So the cells within the soul might and the lateral plate mesoderm are predetermined to form certain structures and then they just go ahead and do that. And then there is a differentiation model where you know, there's a pool of cells and then they differentiate under the effect of various genes and hormones that are expressed in that area which then drive the growth and really are theories lead to sort of a combination of these because all you know, these are all kind of important aspects of the various theories of limb development. So this is what happens from around 4 to 7 weeks. Okay. So you start off with the formation of a small limb buds at the apex. Over here is the typical ectodermal ridge. These are the undifferentiated proliferating cells and this is the polarizing region or the zone of polarizing activity. Um And over time, you have the limbered continues to differentiate and you have cells migrating in, in their forming various structures. So this is essentially what is happening. So the Pike electro dermal ridge that we saw is responsible for the proximal discal growth. Uh This is mainly under acts under the influence of uh F G F. There are various F G F molecules uh And if you have a disruption in that, so where they did studies where they took away the A Pike electro dermal ridge, there was a transverse arrest of the limb at whatever stage of development it was in the radio ulnar differentiation initially is anterior posterior. So the radial side is anterior and uh the ulnar side is posterior is under the influence of the zone of polarizing activity, which is this little red area here that you could see which is on the posterior side. And there is sort of a gradient of hormones. And I have some further images that, that that kind of explain this in more detail. And what they found was that if you messed up the the hormones, so this it's under the influence of sonic hedgehog. And if you mess up the hormonal gradient balance that forms there, you actually get mirroring. So if you have Sonic hedgehog across uh you you have uh you know to radius is or two ulnas and, and the digits look very similar. Um And then there is the dorsal ventral uh orientation which is under uh this W N T uh N grade one which, which are again important molecules. And again, there's sort of a gradient. Uh and if you have disruptions in this, then you have uh you know, double dorsal digits or you have conditions such as nail patella syndrome, uh things like that where the dorsal ventral structures are influenced. So the lateral plate mesoderm is important because that forms the bony structures. And the way bone forms we are aware, you start off with a condensation of mesenchymal cells which then formed the cartilaginous structure or the pre structure of the bone. And then you have vascularization in and you have formation of calcified tissue and you have, you start off with the primary ossification centers and then you have the secondary ossification centers and these continue to form after birth as you're aware. Uh and then they end up forming epiphany Asus and then the articular cartilage. Okay. Um Any questions so far? And you're aware that there are two types of bone formation. One is the intramembranous ossification and endochondral bone formation or endochondral ossification. So, this is an example of endochondral where you have cartilage being replaced steadily by bone. Uh and then you have the flat bones which are forming directly from the mesenchymal condensations within tissue planes. Now, I'm just gonna throw a curveball question, what happens in fracture healing, but it depends on the type of stability you have at the fracture site. Yeah. So, so let's say we are talking about uh healing by second. So by relative stability. So you, you have a fracture that you're treated in the plaster, what sort of ossification takes place there? So you get, you get both uh you get both types of, you get intramembranous and you get an chondral ossification. Yes. So you, you get the bridging callus which is under the periosteum which is kind of direct formation. And then you have the different structures, you know your fibrous and cartilaginous tissue that forms depending on parents strain theory. So you're absolutely right. So your your fracture healing actually brings your bone back to kind of embryonic stages, so to speak. And you have both intramembranous and endochondral ossification. So this is an example of um of what happens when you have disruption of the proximal distal growth. Uh So you have the pike electrodermal ridge and you have the mesenchymal cells uh and the the progress zone. Uh and you have uh you know, kind of longitudinal growth, okay. And over here, this is an example, you know, it's kind of the same picture of the zone of polarizing activity and what you if you have disruptions, you end up getting conditions with short digits. The CPA is important for your radial and ulnar differentiation. So you can see over here that there is a hormonal gradient between sonic hedgehog uh and this G L I three. Uh and there's more influence uh the green up towards the radial side and more towards the ulnar side. And then there's a slight, there's a third one in the mix there. And that is the tee box gene which is responsible for all your radial uh you know conditions that we, we discussed uh just in the last talk there. And so if you knock this gene out, then you will not get any radial structures that are forming. And similarly, uh there is uh there, there are two A S S. So the dorsal side is influenced by the W N T or the wingless N type seven A, uh you know gene expression. And the, the ventral side is influenced by N grade one. And that kind of gives you the dorsal ventral uh differentiation. And if that gets uh messed up, then you have abnormal nail growth and things like that. Okay. So we, we should really be clear with what, what, what you know, when we define or how we define various congenital abnormalities. So, classically, uh we call a malformation uh structural defects uh that in interrupt normal organogenesis. Uh and these can be uh a number of various conditions uh you know, like syndactyly or proximal femoral. So it's again, quite a wide spectrum de formations are uh you know, classically called uh you know defects that uh that, that cause, you know, kind of change shape under mechanical stress, um conditions uh such as Metatarsus, a doctor's and physiological bowing of the tibia. Um you know, Calcaneal valgus. So these, you know, we presume again, these are uh these are theories uh you know that, that they there might be other, you know, genetic preponderance is. But we know in the past, for example, congenital tele PC Coronavirus was clubbed in under deformation. But now we know that there are multiple genes that are involved and it's more a neuromuscular condition as opposed to just a simple deformation, um disruptions. You saw examples of constriction band syndromes or amniotic band syndromes. Uh and then you have dysplasia where there is a uh structural defect caused by abnormal tissue differentiation. And uh the uh it's, it's just that the, the cells uh that are in that organ or tissue are not uh forming that organ as they normally would. And that is quite a large spectrum of conditions that we'll hear about later in form of the skeletal dysplasia as uh those are just the bony, uh you know, and the loads of other types of dysplasia as well. Any questions about these so far? Are they quite descriptive rather than prognostic? Yeah. Yeah. So it's just, it's just to try and uh you know, get some clarity on it, you know, that's all. And in, in the past, we used to use uh Swanson's classification for congenital limb deformities Um And this was fairly apologies if this is repeating because I did not hear uh Kuldeep Stock previously. Uh She has covered this basically, you know, there's failure of formation, failure, separation, this is quite self explanatory. Uh And then for upper limbs, uh this has been uh kind of expanded to uh the OMT the Oberg Man's Tompkins classification. This was published a few years ago. Uh and they tried to uh improve the use, use ability of the classifications. Again, you know, they just ended up making it more complicated. Uh It gives you uh something to work with, I I suppose, you know, so they, they classify conditions mainly as malformations, deformation and dysplasias. Uh And then they have some sub classifications uh in between and uh and they try and differentiate whether their approximate physical uh conditions or radioulnar dorsoventral, trying, trying to go back to the, the original kind of hormonal developmental roots, you know, but again, it's, these are not quite easy to, to put into one particular uh you know, basket or group because the management is not determined by the classification. The management is determined by patient expectations, what you can achieve with the anatomy you have available. So I think this is the most important slide. Uh you know, a lot of these questions come in the, in the M C Q s for the F R C s. And uh I think this is something that, that, that you can be asked. Uh And so, uh this is the main thing to, to kind of leave you with, with regards to the embryology and hope this kind of short talk gave you sort of a good understanding. Uh Great are pools recording, learn.