[0:17]Okay, welcome guys. In this session we'll be discussing about an individual protein that is collagen. What is collagen? What is the use of collagen? How the collagen is synthesized and what are the various collagen disorders that we have? So starting with the first, the basic thing is, uh, the basic point that we can add here is the collagen is the most common protein of body. Most common protein of body. Collagen is there in all the all the structure. You name any structure, the collagen is there. Skin, ligament, tendon, muscle, bone, cornea, hair, nails, everywhere is collagen, everywhere is collagen. So I can say it is present in all the tissue. Present in all tissue. It is the major structural protein, means most of the structure in the body is made up of collagen, major structural protein. The highest concentration highest concentration of collagen is found in skin. Highest concentration is found in skin, followed by cornea. So the highest amount of collagen is found in skin. These are the basic points to be remembered for collagen. It's the most common protein, it's the major structural protein, is found in all the tissue, all the tissue and the maximum concentration is there in the skin. Now, once we have understood this point, let's see the types of collagen. Let's see the types of collagen. When it comes to the types of collagen, again, the list is very long. Around 20 types of collagen we have, around 20 types of collagen we have. We do not have to remember the entire list. We just we'll just write down the important ones that which collagen is found where. So, starting with the first one, the collagen type one. Collagen type one, it is found in bone. Type one is found in bone, skin, ligament, tendon. Collagen type two, it is found in cartilage. Type three, it is found in the major blood vessels such as aorta. Major blood vessels such as aorta. Type four, it is found in the basement membrane. The basement membrane which is there in the kidney, there in the alveoli of the lung. So the basement membrane is the type five, type four collagen. Then, is the type 10, type 10. It is found in hypertrophic cartilage. Hypertrophic cartilage is the type 10. Then is the type 17, that is found in hemi desmosome. Then is the type 19. It is found in rhabdomyosarcoma. It is associated with rhabdomyosarcoma. So there is a such small list that we have made. Although the list is very long. We do not have to remember all the collagen, various type five, six, seven and so on. The first four are the important ones then if you want to remember, you can remember the 10, 17 and 19. 10 in the hypertrophied cartilage, 17 in the hemi desmosome and 19 is associated with rhabdomyosarcoma. This is these are the points to be remembered. Now, Let's see how the collagen is synthesized. The collagen synthesis. Collagen synthesis. The sale which is responsible for the collagen synthesis is the fibroblast. The place is going to be fibroblast. And in the fibroblast, the organelle which is responsible for collagen synthesis is endoplasmic reticulum. So it is the endoplasmic reticulum of the fibroblast, which is the initiating site of the collagen synthesis. So for, uh, for better understanding, what I do is, if I make a fibroblast, say, this is a fibroblast. Here we are going to make the, the collagen inside the fibroblast. Now, till now what we know about the fiber, the collagen is that the collagen is a protein. Protein means what? A chain of amino acid, right? So now the question arises that in collagen, which type of protein we have? Which type of protein we have? So, in the collagen, we have basically three types of amino acid that we have. We are saying that collagen is a protein. Proteins are made up of amino acid. So now the question arises that which amino acid are there. So when it comes to collagen, there are three amino acid which are there. The first one is glycine. The first one is glycine. The second one is, I'm writing as X and the third one, I'm writing as Y. They may be different, but the every third amino acid is going to be glycine. So it will be like this, glycine X Y, again glycine X Y, glycine X Y and so on. So we'll make a chain, we'll make a chain of amino acid and every third amino acid is going to be glycine. The the second and third may be different, but the every third is going to come is the glycine one, glycine X Y, glycine X Y, glycine X Y and so on. Most of the time, this X is replaced by, most of the time this X is replaced by proline. Not always but most of the time, and this Y is replaced by lysine. So if I ask you that which is the most common amino acid, it is glycine. And if I ask you that which are the common amino acid that are found in collagen, then the three options will be there is glycine proline lysine. Glycine, proline and lysine, these are the common amino acid that is there in the collagen. Now, So, I can say that because these three amino acid is going to be repeated for multiple times, so I'm writing glycine X Y into N. They will be repeated for N number of time. So, you will get a linear sequence of these amino acid. And this linear sequence of amino acid of glycine, proline, lysine repeats, this is referred as pre pro collagen. This is referred as pre pro collagen. Now this pre pro collagen is not strong enough to make your bone, to make your muscle, ligament, tendon, right? It is just a chain of amino acid, it's not strong enough to make your bone. So we have to do a certain changes to make it strong enough that it can make your bone, it can make your muscle, can make your ligament, tendon and so on. So, what are the modifications that we are going to do so that it will convert into a strong, stable structure? See, right now the pre pro collagen looks like this. It is having a helical structure, is having alpha helix structure. So, what we do is we take three pre pro collagen molecules, we take three pre pro collagen molecules and we rotate these three pre pro collagen molecule on one another. If we make rotate three pre pro collagen molecule on one another structure will look like this. This is called as triple helix formation. So the first modification that you have did inside the fibroblast is something called as triple helix formation. This is the first modification that we did. Triple helix formation. Then, the second modification that we do is, what we do is, we add the glucose, we add the glucose on the amino acid which are there in the collagen, right? And that is called as glycosylation. We are going to add the glucose molecule, that is called as glycosylation of the amino acid. Then the third thing that we are going to do is we are going to add the hydroxyl group. We are going to add the hydroxyl group, that is called as hydroxylation. Hydroxylation, means we are going to add the OH group. Hydroxyl means the OH group. To do the hydroxylation, to do the hydroxylation, it requires vitamin C. Require vitamin C. If we want to do hydroxylation, it will require vitamin C. Now, when you do all these changes inside the fibroblast, on a pre pro collagen, you make the triple helix, you do the glycosylation, you do the hydroxylation, ultimately this pre pro collagen will be some more, some what more strong, some what more strong and this pre pro collagen will convert into a molecule that is referred as pro collagen. This is called as pro collagen. This is some what more strong than the pre pro collagen, but it is still not strong enough to make your bones. So now this pre pro collagen is converted into pro collagen. Now this pro collagen will come in the extracellular environment. This pro collagen will come in the extracellular environment. So now we are going to do certain changes in the extracellular environment so that it will be more strong, it will be more strong. So what we do is to make it more strong, The first thing that we do is, the first thing that we do is we cleave, we cleave the terminal part, means we remove the terminal parts of the pro collagen. That is called as cleavage of the terminals. Cleavage of the terminals, means whatever is the terminal part, we will remove them out. Now, once you will do that, then we are going to do oxidation process, right? That is called as lysyl oxidase is going to work on these pro collagen molecule. So, lysyl oxidase is going to come and going to work on the pro collagen. This lysyl oxidase requires, requires copper. For the functioning of copper, for the functioning of lysyl oxidase we require copper. Then, the third thing that is going to happen on this pro collagen molecule is something called as aldol condensation. So, once we do all these changes in the extracellular environment, we will remove the terminal part, we treat with the lysyl oxidase, then we do the aldol condensation. So, we get a strong unit. We get a strong unit, that is a quarter strigured unit. That is called as tropo collagen. The molecule that we are going to get is something called as tropo collagen.
[11:14]Now this tropo collagen is a strong unit. Is tropo collagen is like a brick, is like a brick. Now, this is basically a structural and the functional unit of the collagen. Means you want to make different different types of collagen. So what you do is you arrange the tropo collagen in different different manner and you will get the different different types of collagen, right? So this tropo collagen is the main unit, is the main functional unit that is going to be there in all the types of collagen. You just arrange the tropo collagen in different different manner and you will get the different different types of collagen. So I can say tropo collagen is the structural and the functional unit of collagen. By tropo collagen, we will make the different different types of collagen. The different different types of collagen we are going to make from the tropo collagen. So this is how the the collagen is synthesized. This is how the collagen is synthesized. So what are the questions that they are going to ask you from the collagen synthesis part? First thing is which is the most common amino acid? The most common amino acid is glycine. Every third amino acid is going to be glycine. Which are the three common amino acid that are there? Glycine, proline and lysine. Then they ask that what are the intracellular events and what are the extracellular events? The intracellular event, what we do is we make the triple helix, we do the glycosylation and the hydroxylation. Then, the extracellular events is the lysyl oxidase, the cleavage of the terminal part and the aldol condensation. The molecule that we are going to get is the tropo collagen and that tropo collagen is going to make the the various types of collagen. So this is how the collagen is made and this entire process is occurring in the fibroblast. In the fibroblast where? Is mainly occurring in the endoplasmic reticulum. In occurring in the endoplasmic reticulum. So this is how the the collagen is synthesized and these are the questions that they are going to ask that which are the intracellular event and which are the extracellular event. Now, because it is a complex process and it requires a lot of enzyme in the collagen synthesis, sometimes what may happen is that there may be a deficiency of particular enzyme may occur or maybe a particular gene defect may occur so that a particular collagen will not be made properly. If a collagen is not made properly then it will lead to a certain disorders and they are called as the collagen disorders. So, let's write down the list of the collagen disorders. Collagen disorders. So starting with the first one, the first collagen disorder is if let's say the type one collagen is defective. Type one is defective. Type one is found where? It is found in bone. If the type one is defective, it is it will lead to, the bones will be defective if type one is defective means bones are defective, right? So it will lead to something called as osteogenesis imperfecta. It will lead to osteogenesis imperfecta. Osteo means bone, genesis means formation, imperfecta means imperfect. So the bone formation will be imperfect if the type one collagen is defective. If the type one is defected, it will lead to osteogenesis imperfecta. What are the points, what are the points to be remembered for osteogenesis imperfecta is, if we talk about the clinical feature, these childs will have something called as blue sclera. Blue sclera. Now what is the meaning of blue sclera? See, normally this white part of the eye is called as sclera. The white part of the eye is called as sclera. But in these patient of osteogenesis imperfecta, what happens is that the sclera is very thin, sclera is very thin. So, behind the sclera, we have the the veins which are there and these veins are visible from the outside, right? Normally the veins which are there, the choroid plexus, which is there behind the sclera, it is not visible right now in my eyes, it is not visible. But if the sclera is very thin, the white part of the eye is very thin, the choroid plexus reflex will come outside and that reflection that you are going to see, it will give the bluish discoloration of the sclera.
[15:41]So this is one of the feature that we should know regarding the osteogenesis imperfecta that is blue sclera. Now coming to the the second disorder. The second disorder is if the type two is defective. Type two is defective, type two collagen is found in cartilage. Type two collagen is found in cartilage. If the type two is defective, it will lead to, the cartilage will be defective and that is called as chondrodysplasia. Chondro means cartilage, the cartilage are going to be defective, so that is called as chondrodysplasia. Chondrodysplasia. Then the next one is the type three. If the type three is defective, it will lead to, see type three is found in major blood vessels. Type three is found in major blood vessels. If it is defective, it will lead to something called as Ehlers-Danlos syndrome. Ehlers-Danlos syndrome. Now what is Ehlers-Danlos syndrome? See in Ehlers-Danlos syndrome, almost all the type of collagen is defective. Almost all the types of collagen is defective. But if you have to select one then you are going to select the type three. So I'm writing the statement that Ehlers-Danlos syndrome, almost all the types of collagen are defective. Almost all the type of collagen are defective, but if you have to select one that which is the most specific, most specific then you will see the type three.
[17:15]But most specific is type three. Because rest can be defective in other disorders, but the type three if it is defective, then it is going to worth the the Ehlers-Danlos syndrome only.
[17:32]Ehlers-Danlos what happens is as I am saying that almost all the collagens are defective, the person will have hyperelastic joints. The hyperelastic skin will be there, right? So he will be able to do or he will be able to move the the joints more than the normal range of the motion. So this Ehlers-Danlos syndrome is also referred as rubber man syndrome. It is also, also called as rubber man syndrome. So if I show you the image of rubber man syndrome. This is the image of rubber man syndrome, this is the image of rubber man. You can see that this normal, normal healthy individual cannot do like this, right? This is the hyperelastic joints which are there. The range of the motion of the joints is increased and this is seen with Ehlers-Danlos syndrome. If the type four collagen is defective, type four is found in the basement membrane. If the basement membrane is defective, it will lead to something called as Alport syndrome. It will lead to Alport syndrome.
[18:35]Alport syndrome. The classical triad of the clinical feature is important. It will lead to hematuria. It will lead to sensory neural hearing loss and it will also lead to something called as anterior lenticonus. Anterior lenticonus. So the classical triad of the symptoms that you are going to see in a patient of Alport syndrome.
[19:04]The patient will have hematuria. The basement membrane is defective, it will lead to hematuria. There will be hearing loss and this is the sensory neural type of hearing loss. We have discussed one more condition where we have the sensory neural type of hearing loss, that was the Pendred syndrome, that was there, if you remember along with the hypothyroidism, the iodine receptor, the pendrin was not working, right? So here also we are going to have the sensory neural hearing loss along with there will be lenticonus. Now what is lenticonus? See, normally, if I, if I just give you a simple diagrammatic representation. Let's say this is the cross section of the eyeball. Cross section of the eyeball. And this particular part is your cornea, right? There is a curvature of the cornea we have, the black part of the eye, this is the cornea and that we have a curvature on that. Now, if there is excessive curvature. If there is excessive curvature, let's say the diagram looks like this. Now what you can appreciate is that the curvature of the cornea is increased excessively on the anterior side. This excessive curvature of the cornea on the anterior side is called as anterior lenticonus. So what is lenticonus is, excessive curvature of cornea. This excessive curvature of the cornea is referred as the anterior lenticonus. So that is the the Alport syndrome. That is the Alport syndrome. So we have discussed about the type one disorder, that is that will lead to osteogenesis imperfecta. Type two, if it is defective, it will lead to chondrodysplasia. If the type three is defective, it will lead to Ehlers-Danlos syndrome. The point to be remembered is in Ehlers-Danlos almost all the collagens are defective. Almost all the collagens are defective, but the most important or the most specific one that is going to be there is the type three. Then is the type four, if it is defective, it will lead to Alport syndrome. The classical triad is very important. They will give you a clinical scenario and they will ask that what are the what are the symptoms that are going to be there. The hemuria, sensory neural loss and the lenticonus is going to be there. So, these are the the collagen disorders. If the collagen synthesis is not proper then the defective collagen will accumulate in a certain organ and will lead to the certain features that is called as the collagen disorders. Now sometime what happens is the collagens are made completely fine, completely fine. But the immune systems are not working properly and they are making antibodies against a certain type of collagen, right? If antibodies are made against a certain type of collagen, then that particular collagens are going to be, uh, we can say will not be working properly. They will be destroyed continuously by the immune system and they are the autoimmune collagen disorders. They are the autoimmune collagen disorders. So, here I want to discuss the first disorder that I want to discuss here is with the name of Goodpasture syndrome. Goodpasture syndrome. Now what is Goodpasture syndrome? Goodpasture syndrome is, there is auto antibodies, there is auto antibodies against the basement membrane. Basement membrane is the type four collagen.
[22:31]Collagen is completely fine, type four collagen is completely fine, but the immune system is misdirected, misdirected. So, how the patient will come to you is, the clinical feature the patient is going to have is, he will have hematuria because the basement membrane is the kidney is destroyed. As well as will have hemoptysis, means there will be blood in the sputum. Blood in the cough that is hemoptysis and the hematoria is going to be there. This is the first one that is the Goodpasture syndrome. Then the the second one is the something called as the bullovesical disorders. Bullovesical disorders. To understand the bullovesical disorder, first we need to understand a simple, uh, we can say histology details of the epidermis and the dermis. See, the epidermis is having five layers. Epidermis is having five layers. How we can remember is with the mnemonic college C L G college bus. College bus. These are the five layers. The lowermost is the stratum basale and I am right now concerned with the stratum spinosum. That is the stratum granulosum, stratum lucidum and stratum corneum. The stratum corneum is the uppermost and the stratum basale is the lowermost in the epidermis. These are the layers which are there in the epidermis, stratum corneum, lucidum, granulosum, spinosum and basale. Now, when it comes to the dermis. When it comes to the dermis, in the dermis we have two layers. One is called as the papillary layer. Papillary layer and the reticular layer. Reticular layer. So the point I want to convey to you is that the space which is there between the epidermis and the dermis.
[24:49]There is a space between these two. This is the sub epidermal area. Beneath the epidermis sub epidermal. So the stratum basale, or I can say the epidermis is uniting with the dermis with the help of one structure and that is the hemi desmosome. This yellow color structure which I'm making, these are the hemi desmosomes. These are the hemi desmosome, which are joining the, which are joining the epidermis with the dermis. These are the hemi desmosomes. Because we are discussing hemi desmosome, so here itself I want to add a a related topic that is desmosome. So in the stratum spinosum we have the sale linings. We have the sale linings. The sales of the stratum spinosum is held together with one another with the help of a structure and that is called as desmosome. So now we have the orientation that where is desmosome and where is hemi desmosome. Desmosome is there in the epidermis, right? It is in the stratum spinosum. The sales are joined by that. Whereas hemi desmosome, it is between the epidermis and the dermis. There is a link between them, that is the yellow color molecule in the diagram, that is the hemi desmosome. Now, once we have this orientation, once we have this orientation, now sometime what happens is that the auto antibodies are formed against these molecules. So, let's say there is auto antibody against against hemi desmosome. If there is auto antibodies against hemi desmosome, this is referred as bullous, this is called as bullous pemphigoid. That is called as bullous pemphigoid.
[26:45]That is called as bullous pemphigoid. Whereas if there is auto antibodies against desmosome.
[26:56]This is called as pemphigus vulgaris. That is referred as pemphigus vulgaris. So depending that which structure is getting destroyed, if it is hemi desmosome it's called as bullous pemphigoid, if it is the desmosome that is called as pemphigus vulgaris, right?
[27:16]Now what are the things that they ask in the exam regarding these two disorder, the bullous pemphigoid and the pemphigus vulgaris. What they ask is where is the lesion on the biopsy? Where is the lesion? On the biopsy. If you take the skin biopsy, in the bullous pemphigoid, if I ask you the question that in bullous pemphigoid, the hemi desmosomes are getting destroyed. So looking at this diagram, looking at this diagram, if I say that, the hemi desmosomes are going to be destroyed like this. Like this. The, the antibodies are going to be accumulated here and this will be called as the bullous pemphigoid, BP, bullous pemphigoid. So where is the lesion? Where is the lesion? Sub epidermal, sub epidermal. Whereas in the pemphigus vulgaris, the desmosomes are going to be destroyed like this. This is the pemphigus vulgaris, PV. Where is the lesion? Inside the epidermis. So they ask that which is having intraepidermal and which is having subepidermal lesions on the biopsy.
[28:28]In the pemphigus vulgaris, I want to add one more point that in the pemphigus vulgaris, the acantholysis is seen in pemphigus. Whereas in the bullous pemphigoid, there is no acantholysis. Acantholysis is present, not present. See, what is acantholysis? Acantholysis means if the stratum spinosum cells, if the stratum spinosum cells, they are loosen apart. If the stratum spinosum cells they loosen apart, that is called as acantholysis.
[29:04]Acanth word is used for stratum spinosum. Acanth word is used for what? It is used for the stratum spinosum. If there is lysis in the stratum spinosum, it's called as acantholysis. Acanth for spinosum if there is lysis is called as acantholysis. So acantholysis is going to occur where in the pemphigus vulgaris. Acantholysis is not a feature of bullous pemphigoid, right? So this is one thing that they ask. So these are the bullovesical disorders that we should know. Uh, when it comes to the autoimmune disorders of the collagen, we have discussed the Goodpasture syndrome. Then we have discussed about the bullovesical disorder. In the bullovesical, we have discussed about two, that is the bullous pemphigoid and the pemphigus vulgaris. So these are the points, uh, to be remembered when it comes to the autoimmune disorder of the collagen, uh, in the collagen. Now, the last one, the last collagen disorders that I want to add here is, see in the extracellular environment I told you that when we are making the collagen, we use an enzyme that is called as lysyl oxidase. If I just scroll up the notes so that you will be able to correlate. This is the collagen synthesis pathway that we have used and here we have used one enzyme that is with the name of lysyl oxidase. With the name of lysyl oxidase. If this lysyl oxidase is defective, right? That will lead to a disorder that is called as Menke disease. That is called as Menke disease. So let's write down this point. Defect of lysyl oxidase will lead to Menke disease. Menke disease. Menke disease. So these are the various collagen disorders. If the collagen itself is defective, if the enzyme is defective or the auto immune disorders are there, right? Thank you guys.
