foreign what's up Ninja nerds in this video today we're going to be talking about hyperlipidemia this is a part of our clinical medicine section if you guys like it helps you please support us one of the ways that you can do this by hitting that like button you can also comment down the comments section if you'd like and hit that subscribe button if you really like our video content also I really urge you guys go down the description box below there's a link to our website we have a lot of great things that we offer there that we don't have on our YouTube such as notes illustrations questions we're developing actual exam prep programs for those of you taking your exams your board exams also we got some Ninja kind of Swag glue that you guys could check out so please take some time and go look at that if you'd like hyperlipidemia what is the problem with this well you can Define this a lot of different ways right A lot of the times hyperlipidemia is the most common terminology that we utilize and oftentimes it really consists of an abnormality within some of the lipoproteins or lipid molecules within our bloodstream I think what's really important when we're talking about these is to understand the particles that are truly involved in the disease process that we see with hyperlipidemia so one of these is a really problematic molecule here and this is called LDL so LDL is one of these molecules that if you have really really high amounts of LDL it really can be associated with a lot of atherosclerotic plaques which we'll talk about as the complications of hyperlipidemia so this is not a very good one to have high amounts of that's one way that we could Define hyperlipidemia or dyslipidemia another molecule that is also super important in kind of the process of lipid transport and a lot of the things that are going on there is a molecule called HDL now a lot of people neglect HDL but HDL is super important because it's one of those guys that's primarily proteins and phospholipids and it kind of helps to scavenge and pull some of the cholesterol and fat away from the peripheral tissues such as the blood vessels which helps to reduce a lot of atherosclerosis so if a patient has very very low HDL levels this also is a problematic issue however when you hear the term hyper you don't commonly associate that with a low level of a molecule you associate with the high levels of a particular molecule but just remember in your head that in hyperlipidemia it can be high LDL or low HDL sometimes we use the terminology here where someone has high LDL and low HDL will use the terminology dyslipidemia because there's an abnormal process or abnormality within the actual lipid particles last one here is going to be you got this glycerol with the fatty acids hanging off of it what's this bad boy this is the triglycerides these are also problematic They Don't Really carry that same exact intense risk of atherosclerosis but they do carry a pretty high risk of tissue deposition particularly the liver the pancreas and then cause a lot of Havoc there as well so when you think about hyperlipidemia what you're really thinking about is patients who have very high levels of LDL which carries lots of cholesterol deposit that into blood vessels low levels of HDL they don't remove some of that plaque from the blood vessel wall or high triglycerides a lot of soft tissue and visceral organ deposition all right cool question that arises okay how do I get lots of LDL in my bloodstream how do I get lots of triglycerides in my bloodstream that lead to these disease processes well one is it unfortunately could be inherited not the best ideal thing but inherited hyperlipidemias you want to think about in the young kind of patients or patients who are like getting their blood work done and you just keep noticing that their blood levels their actual cholesterol levels their LDL their triglycerides are massively elevated despite therapeutic measurement uh measures okay so first one is we have type one and type 1 the primary disease process here is that you have a defective L uh what's called lipoprotein lipase this is an enzyme and we're not going to go into the crazy depths of this because we covered in our actual pathology lecture here we're going to kind of be kind of basic here but there's a defect within the LPL the lipoprotein lipos we'll put a down arrow here what it's supposed to do is take molecules called chylomicrons and when it takes these chylomicrons it can do this for my chylomicrons and sometimes also for vldl particles it's supposed to help in ripping some of the triglycerides from the chylomicrons and having them being taken up because it breaks down the triglycerides into free fatty acids so that's what it's supposed to do but in this process there's a defect within this LPL and it doesn't allow for that process to occur so what is chylomicrons carry a lot of triglycerides so what happens is is that these patients develop crazy crazy high levels of chylomicrons like insanely high levels and chylomicrons are what rich in they are rich in triglycerides and so what these patients develop is crazy crazy crazy high triglyceride levels because you're supposed to in these patients take the chylomicrons which contains the triglycerides rip them apart in the free fatty acids and the free fatty acids are taken up by the adipose tissue in the muscle but it doesn't occur here that's one potential way that you can develop hyperlipidemia so again type 1 is one of those disorders now type 1 usually what happens is there is a mutation and the easy way to remember this is that it goes recessive dominant recessive dominant okay so this would be a autosomal recessive disorder that leads to A lipoprotein lipase mutation altering chylomicrons from being degraded they end up accumulating and increase your triglycerides boom hyperlipidemia type two we already said autosomal recessive so this has to be autosomal and dominant in this disorder there is a defect in the LDL receptor all right so the LDL receptor is the problem here so we're going to put that there is some type of defect here or decrease activity of this receptor what this receptor is supposed to do is take LDL particles and do what bind onto them and bring them into the liver to use the cholesterol from the LDL make particular types of molecules but it's not going to and because of that what happens as a result is if this process does not occur now what result is the LDL stays elevated within the bloodstream and if LDL remains elevated within the bloodstream it carries tons and tons and tons of cholesterol with it so what happens to the patient's cholesterol levels they really go through the roof and so what you'll notice is that these patients will have insanely High total cholesterol levels because they have insanely high LDL levels so type 1 high triglycerides type 2 high LDL leading to an elevated total cholesterol also more recessive autosomal dominant all right type 3 and 4. all right for this one it's also a mutation recessive dominant recessive dominant let's write these out so for this one it will be also more recessive autosomal dominant nice way to remember right now when we talk about these in type three this one's a weird one so in type 3 there is a defect within What's called the apoe protein so there's a protein here you see on these guys so this is called the APO e protein this April here we'll put like a little hyphen here to really kind of to note that this is a specific type of April protein so apoe is defective so what we're going to do is we're going to put like an X there all right what apoe is supposed to do is it's supposed to take particles like what greater than that you asked that it's supposed to take things like chylomicron remnants and vldls and uptake them but that will not happen so what ends up happening is you have these things called vldls which carry lots of triglycerides and cholesterol and kylo Micron remnants which carry lots of cholesterol but really lots of triglycerides because you can't take these bad boys in guess what ends up happening you end up accumulating things like these and if you have lots of vldl and lots of we're going to abbreviate these kylo microns we're going to put kylo here remnants these carry lots of cholesterol and lots of triglycerides and so what happens is these patients develop very high triglyceride levels and very elevated cholesterol levels and that's what you'll see as a result of this is they'll have lots of these vldls and chylomicron Remnants and subsequently lots of triglycerides and lots of cholesterol so if I said massively increased triglycerides you'd say type 1. if I said massively increased LDL you'd say type 2.
if I said increase chylomicron remnants in vldl which causes both cholesterol and triglycerides to go up you'd say type 3. that is the difference here with this one lipoprotein lipase mutation LDL receptor mutation able e mutation for the last one here this is a very interesting one your liver is supposed to produce this molecule called vldl right so supposed to make a molecule called vldl which carries lots of triglycerides Clio microns and vldls carry lots of triglycerides LDL particles carry tons of cholesterol so what happens is in this particular scenario there is a increased synthesis so we're going to write here a increased hepatic synthesis of vldl for some particular reason when that occurs vldls are in massive amounts and what they will do is is they will increase the triglycerides pretty substantially so now you're kind of in a situation where you're like okay which one how would I differentiate these again autosomal dominant for Type 4 has massive hypertriglyceridemia type 1 which is an autosomal recessive has massive hypertriglyceridemia one of the ways that they try to tip you off in the exams is when you look at the actual blood when you take a sample of blood from these patients if it says a creamy kind of like layer on the top of the blood sample that's usually indicative of heavy amounts of chylomicrons as compared to the increased vldl causing triglycerides to be super high this is how we would talk about the causes of hyperlipidemia when it's inherited all right so let's start talking about acquired hyperlipidemia now within this this is usually disease States or drugs that are causing this particular process so first one diabetes is a big one what happens is is you have this molecule this enzyme here which we already talked about called lipoprotein lipase now it does help with breaking down chylomicons remember I told you there's another molecule that helps to break down the triglycerides vldls remember vldls and chylomicrons are rich in triglycerides so they have the apoc2 protein to bind with LPL again we'll talk about that more in the actual pathology lecture but if we take this guy here which is our vldl he should be naturally having triglycerides ripped away by the LPL metabolized by adipose and muscle but what happens is in patients who have diabetes they have some type of problem with their insulin maybe it's insulin resistance maybe it's a decrease in insulin because of an actual disease process whatever it may be there is a decrease in the effectiveness of insulin if there's a decrease in the effectiveness of insulin what happens now is that this leads to the inhibition or the decrease in the activity of this enzyme can this enzyme now take and rip away the triglycerides and convert them into fatty acids no so what happens is is as a result vldls begin to accumulate and vldls can easily convert into another molecule so now you're going to end up with an increase in vldl and you know um VL deals that have virgin triglycerides but you know that VL deals a lot of them convert eventually into LDL so you'll also see an increase in LDL so totally you could see an increase in triglycerides and an increase in cholesterol in this patient population who have diabetes boom roasted hypothyroid related in this scenario when a patient has hypothyroidism they have less of what's called T3 nt4 now T3 and T4 are interesting when they're made by the thyroid what happens is they're supposed to go to the liver when they go to the liver they're supposed to maintain the expression of the LDL receptors but that doesn't happen now if you don't have them so the LDL receptors are now down regulated if you don't express these LDL receptors can you bind LDL no and so now this is supposed to bind here but it doesn't happen and if it doesn't happen the LDL molecules will build up within the bloodstream and if LDL builds up in the bloodstream this will effectively increase the patient's cholesterol precipitating hyperlipidemia all right we come into the last disease State here which is called nephrotic syndrome now nephrotic syndrome is a really cool mechanism here there's a disease where the glomerular filtration barrier particularly the podocytes are damaged and they're having a hard time being able to maintain the loss of protein so these patients lose tons and tons of albumin in their urine so we call the albumin urea you can also see this in CKD but what happens is when you have all this albumin area as a result you don't maintain as much album with in the blood and so the albumin within their bloodstream is low now who is the organ that makes albumin deliver so what this does is this cells deliver hay buddy albumin is pretty low start making proteins but unfortunately the liver doesn't really know the difference and it starts making a bunch of different types of proteins and unfortunately some of those proteins that it decides to synthesize here is going to be vldl and LDL and these puppies will increase and the patient can develop hyperson triglyceridemia hypercholesterolemia and again there is the disease process there is some medications that are also involved here the mechanism as the how they do it isn't completely known but you have beta blockers you have oral contraceptives thiazide diuretics those also can trigger hyperlipidemia all right with that all being said now we have to come to the point is if a patient has hyperlipidemia elevated LDL elevated triglycerides low HDL what are the complications that can arise I'm a friend we have a patient who has hyperlipidemia what are the complications that can arise well the first one is atherosclerosis by far really big risk factor remember atherosclerosis can be due to smoking it can be due to Advanced age diabetes it can also be due to cholesterol problems and it can also be due to hypertension and family history but cholesterol problems is a big one and particularly I'd say the most problematic one is going to be the LDL yes triglycerides can contribute to this but by far it's going to be the Super elevated LDL molecules what's going to happen is that and I would also go as far as to say low HDL but for right now we talked about all the disorders that lead to an increased LDL inherited primarily type 2 right and then we can see this really in all of the acquired types right because of this as the LDL goes pretty high what's going to happen is is this going to lead to atherosclerosis these plaques that develop within the vessel walls when atherosclerosis develops it can develop in vessels a very vital organs such as the heart and the Heart of these plaques occur they can cause ischemia to The myocardium potentially something that coronary artery disease and worst case scenario that can cause infarction of The myocardium such as antimicardial infarction the other thing is it can cause a transient ischemia of the actual cerebrum so we don't perfuse the brain vessels as well and you can develop a TIA worst case scenario these patients can develop CVA a complete infarct or stroke the last one here as you develop ischemia to the lower extremity so this can develop something like peripheral artery disease but if the peripheral artery disease continues to progress because you plaque up these vessels and narrow the actual blood flow sometimes these patients can develop things like critical limb ischemia or if you cause a thrombosis of the plaque in these actual vessels it may lead to an acute limb ischemia so you can see how just having super elevated LDL or low HDL in patients regardless of their cause can lead to atherosclerosis over time and the consequences Downstream from that pancreatitis is heavily heavily associated associated with high triglycerides so when I talk high triglycerides I'm talking crazy high so I'm talking like you can definitely see this in patients with type 1 or type 4 inherited hyperlipidemia and you can see this in really a lot of acquired hyperlipidemics especially those with very very poor diets what happens here is it needs to generally be at least greater than or close to a thousand milligrams per deal when that triglycerides are that high they can activate pancreatic enzymes and lead to pancreatitis and obviously pancreatitis can lead to massive pancreatic inflammation which you want to watch out for so many complications for but epigastric pain and a patient who has massive hypertriglyceridemia maybe with some Associated nausea vomiting and other Associated complications definitely think about pancreatitis all right my friends now the last situation here is steatosis this is fat accumulation within the liver and patients who have very very high lipid levels I'm talking super high LDL super high triglyceride levels what happens is this fat really deposits heavily within the liver and when it deposits heavily into the liver it leads to something which we call steatosis which is just kind of like a fatty liver if you will what happens is this steatosis can activate inflammatory cells these inflammatory cells will then come in and Trigger inflammation of the steatotic liver when you inflame a liver now it's fat Laden and inflamed this is called steato hepatitis now the last particular scenario that can result in this is why it's so important to get a hold of this is that then you can start laying down fibrous tissue and when you laid on fibrous tissue this is irreversible loss of actual liver function and this will start leading to a patient developing something like cirrhosis this is super common in patients who'd have what's called non-alcoholic stiato hepatitis or non-alcoholic fatty liver disease where they have intense hyperlipidemia that can literally lead to cirrhosis the last things that I want you guys to talk about I don't have it here but are going to be soft tissue deposition so sometimes when your cholesterol is really high your triglycerides are really high these actual molecules can deposit into the tendons and lead to something called xanthomas another thing is it can deposit into the actual tissue on the medial side or the nasal side of the eyelids we call that xanthelasma and the last thing is sometimes a lot of triglycerides can deposit around the cornea and precipitate something called a corneal arcus given these findings these are the biggest things that I want you guys to remember for hyperlipidemia but now that we've talked about it let's go over the actual diagnostic approach so the next thing is okay we have a patient who comes in maybe they have some xanthomas some xanthelasma maybe they have an underlying history of atherosclerotic cardiovascular disease maybe they have some underlying steatosis that was found incidentally on an ultrasound or a CT scan or they have pancreatitis for whatever reason you have some things that are definitely cueing you in here so you're going to go ahead and approach how to diagnose this and then subsequently how to treat well the first thing that you have to be able to ask yourself when you're treating hyperlipidemia are trying to diagnose it even in general is are they going to require Statin therapy stats are the primary therapy for hyperlipidemia regardless of the type and when you think about this there's about four reasons why you would do this one is do they have clinical atherosclerotic cardiovascular disease in other words do they have evidence of CAD do they have angina have they had any evidence of Mis have they had a Tia have they had a stroke do they have peripheral artery disease or have they have any events of acute lymph ischemia or critical ischemia if that is the case or even do they have aortic aneurysms that were incidentally found if that is the case they need to be on Statin therapy it's super important is there LDL greater than 190 because they're at super high risk for atherosclerotic cardiovascular disease so that's again another indication the third one is do they have diabetes diabetes is a huge risk factor for a lot of vascular diseases but on top of that when your age starts increasing to at least 40 to 75 and the LDL is greater than what we would want especially 70 your risk of atherosclerosis and disease processes increase significantly so these patients need statins and lastly is the patient who's not a diabetic but their atherosclerotic cardiovascular disease risk comes out to be greater than or equal to 7. 5 percent and the way that we determine that is we plug it into a calculator and it looks at a lot of different risk factors but the whole point is what's the 10-year risk of a patient developing a stroke or am I because of their hyperlipidemia or other risk factors and this is going back to that sad CHF thing so this is the mnemonic to remember for atherosclerosis smoking is a big risk factor age is a big risk factor diabetes high cholesterol especially increased LDL I mean even low HDL which is important to remember and hypertension in a family history of underlying you know vascular diseases so if that is the case and you find that that risk is greater than or equal to 7.
