what's up everybody in this video i'm going to be talking about cartagoner syndrome this is also known as primary ciliary dyskinesia this is brought to you by dirty medicine before i get into today's video if you want to support my channel financially and help contribute to my mission to provide free quality medical education please consider clicking the join button if you click that button you'll sign up to be a dirty medicine member in which you'll pay 4.99 a month in financial support of my channel you can click the first link in the description of any video or click the join button which is located underneath every video or on my channel homepage your support is very much appreciated and i thank you for your consideration now in this video we'll be talking about cartagenar syndrome again also known as primary ciliary dyskinesia and when it comes to this disease on usmle or comlex the reason that this is pretty high yield is because it allows test writers to ask you lots of questions about associations to this disease so what they could do is they could ask you for the genetic cause of this disease they could give you the disease presentation and ask you to differentiate this disease against other similarly sounding presentations or similarly sounding diseases they could ask you for the molecular or cellular basis of this disease they could give you radiographic images because there's one that's very high yield that shows up a lot there's just a lot of different directions they can go with this and test writers love topics where they can do that because it allows them to ask you second and third order questions so with that said let's just jump right into this topic by the end of the video you'll know everything that you need to know in order to get 100 of your questions correct so let's start by talking about the genetic cause or the genetic basis of primary ciliary dyskinesia so the genetic defect occurs in dna l1 or the dna gene and these genes code for products known as the dynein light chain 1 and dynein heavy chain 5. so if you look at this image this is a rough overview of the composition of the microtubule and then it gets more microscopic so you're kind of looking in a of the whole arrangement of the microtubules and then in b we've got a cross-section of a modal cilia and then at c we're kind of zooming in on where that red arrow is pointing and then for d we're looking microscopically at the light chains and the heavy chains of the dynein arm now recall from your first year of medical school that dynein is really a family of cytoskeletal motor proteins and they're responsible for helping the movement along microtubules in cells now what these dyneins do is that they take chemical energy which gets released from the hydrolysis of atp and they convert that chemical energy into mechanical work and that mechanical work is a very fine-tuned alternating sliding that occurs in the light blue and dark blue that you see where this red arrow is pointing to and as those light blue and dark blue sections slide against one another they propel and fine-tune and coordinate motion at the microtubule which you'll recall is a very crucial element of proper ciliary and flagellar if that's a word flagella movement so as you can see the defect in primary ciliary dyskinesia is that those little teeny products the light chain 1 heavy chain 5 are defective and therefore the microtubules cannot fine tune their sliding and therefore you have impaired motion or impaired motility of the microtubule and therefore the cilia flagella so with this in mind it's really easy to think about the symptoms of primary ciliary dyskinesia if you can remember that the problem is with ciliary motion so if ciliary motion doesn't work then basically anywhere in the body that cilia are needed there's going to be a problem so let's run through some of these high-yield symptoms now the first big one is recurrent pulmonary infection now recall that cilia are these little hair-like attachments on epithelial surfaces and specifically these surfaces line things like the nasopharynx the lower respiratory tract the paranasal sinuses the middle ear etc so in the respiratory tract throughout the entire respiratory tree if there's abnormal ciliary movement then you're not going to get that very much needed mucociliary clearance and therefore if you can't use mucociliary clearance you're going to get recurrent and sometimes chronic cynopulminary infection the next major symptom is infertility and although medical students classically associate this only with males in this disease it actually can also happen to females as well now recall that in this tale of the sperm and in the fimbriae of the fallopian tubes there are cilia so for males the sperm is immodal and for females because the fimbriae of the fallopian tube the cilia is not working to sort of usher things along this can increase the risk of ectopic pregnancy and also cause female infertility so in both males and females infertility is a big problem the last major high-yield symptom of primary ciliary dyskinesia is situs inversus and situs inversus is basically like a flip-flopping of the thoraco abdominal orientation now it's interesting because the reason that this occurs is that in embryogenesis you actually need modal cilia in order to get the right thoraco abdominal orientation so in about half of the patients that have primarily primary ciliary dyskinesia they'll have this situs inversus because normal ciliary motion is needed for the proper formation of this thoraco abdominal viscera so without it things don't migrate correctly and therefore you can get this flip-flopping in embryogenesis now some of the other symptoms that you could see in the clinical vignette are a little bit less high yield but i just want to point them out and take a moment to explain that they're not necessarily primary symptoms but they're actually sequelae of these things that you see here so the first one is conductive hearing loss and it's not necessarily that people with primary ciliary dyskinesia have primary conductive hearing loss but with recurrent otitis media and middle ear effusions that occur chronically you get the sequelae of possible conductive hearing loss so if you see that in the vignette that could still be hinting at primary ciliary dyskinesia the other thing that you want to look for because of these chronic pulmonary infections in the respiratory tree would be something like nasal polyps so when you're taking us emily and comlex you can see these additional sequelae again not necessarily being primary symptoms of the disease but being secondary to the recurrent pulmonary infections now i want to just take a moment to also talk about how the test will make you choose between either primary ciliary dyskinesia and then other very similarly presenting diseases and the biggest one is cystic fibrosis so you want to keep in mind how you reason through your differential diagnosis clinically speaking so what i want to do is just put some stuff on this slide what you'll see in red are going to be the overlapping symptoms between cystic fibrosis and primary ciliary dyskinesia and what you see in blue is unique to cystic fibrosis so the reason that it's hard to pick between cystic fibrosis and cartageners is because both of those diseases will have recurrent pulmonary infections both of those diseases will have infertility in males and both of those diseases might have nasal polyps now recall that in the case of cystic fibrosis the infertility in males is due to the congenital absence of the vas deferens so the cause is different but the end result is functionally the same the men are still infertile and for the recurrent pulmonary infections in cystic fibrosis remember that if the test is going to go after that usually what they'll do is ask you specifically for the causative pathogen that's a very high yield micro topic so you want to know that in early infancy usually that would be due in cystic fibrosis due to staph aureus in adolescence that would be due to pseudomonas um and then if they were gonna give you a chest x-ray for cystic fibrosis you're going to look for that reticulo nodular pattern with sinus opacification so those are like the the subtle differences but just remember that recurrent pulmonary infections doesn't necessarily delineate cystic fibrosis from cartagenar syndrome now because of this the test writer needs to give you specific buzzwords or specific clues if they want you to pick cystic fibrosis because obviously there'd be no other way to rule out cartagena syndrome so what you see in blue on this slide is what they'll probably give you if they want you to pick cystic fibrosis so the first big one is pancreatic insufficiency and this could be presented to you clinically with a fat soluble vitamin deficiency and remember that those are vitamins a d e and k the other thing that the test writer could go after is the genetic cause because obviously the genetic cause of cystic fibrosis is different from cartagoner syndrome and in cystic fibrosis that's a defect in the cftr gene which is located on chromosome 7. now they could also give you the diagnostic workup to get to cystic fibrosis so they could describe the sweat test to you that's a big one and then lastly they could give you some physical findings such as nail clubbing or meconium ileus in a newborn now those are the the symptoms and the things that they could describe specific to cystic fibrosis and then of course if they give you something like situs and versus they're telling you that they're actually going after cartagena syndrome so knowing all of the associated stuff helps you delineate cystic fibrosis from cartagenar syndrome because they have those really big overlapping overlapping features but that's it for this video uh it was a quick one kind of rapid review i just wanted to run through what i thought was a really high yield disease process point out the high yield symptoms and then differentiate it from the other disease that sounds a lot like it so keep this in the back of your mind keep the associations and the buzzwords in the back of your mind so you can create that neural network and expect what the test writer might ask you if they want you to answer a question about this disease