iein engineers in this video we are gonna talk about the histology of the liver if you guys haven't already go see our video on the vascular supply or the circulation of the liver as well as the portal hypertension video we go into more of the gross anatomy on the liver we talk about the blood supply to the liver and then what we did is we kind of finished off that video talking about what's called a liver lobule and that's what we're gonna try to focus on a lot in this videos we're gonna really zoom in into the structure of the liver and to look at it at the actual tissue and cellular level alright and then after that we'll have another video and we'll focus that it specifically at the cellular level alright so let's go and get started alright guys so now what we're gonna do is we gonna really really zoom into the liver okay there's this special structure that we're going to talk about we're gonna really zoom into it if you guys remember the end of the video we kind of around the time were we talking about the liver circulation and we're talking about portal hypertension we talked a lot about the blood flow to the liver remember we talked a lot about the blood supply and we said the main blood supply we're not going to go into a lot of detail because we've already covered it but the main blood supply to the liver was coming from the apat ik artery proper right so is this artery right here called the Apothecary proper and we said that thing a patek artery proper was important because what it was responsible for doing is is it's responsible for supplying oxygen-rich blood to the liver okay supplying a lot of oxygen-rich blood then we said that there was another one so again before we shouldn't spend that next one what was this one right here called it was called the a' patek artery proper okay then after that we had another guy and that one was really important because we said that that was applying 75% of the blood flow to the liver right over the blood supply right and that was coming from your gastrointestinal tract and this one was called your portal vein if you remember the portal vein was bringing blood from a bunch of different structures from your gastrointestinal tract and that portal vein this is your portal vein it's bringing nutrient-rich blood okay nutrient-rich blood and I might even contain toxins and might contain bacteria might contain drugs it might contain alcohol a lot of different things but the whole important thing is that this is providing 75% of the blood supply to the liver seventy-five percent and then the Apothecary proper is only supplying a very small minimal amount that being approximately 25 percent of the blood supply to the liver all right now we said that there was another really important structure that was coming in to the liver or specifically I should actually be more specific draining the liver remember there's these special structures here that drain the liver and they contain a lot of bile right they contain by own bile is important for a multiplication of lipids it's also important because a lot of the things that we actually our liver metabolizes if it doesn't want it in the body can actually excrete it out of the body in the bile so that's important so this structure here we said is the bile duct and we'll go over the biliary system in an individual video for right now I just want you to know that this is the significance here so there's three specific structures that are coming through that porta pottis the ones that are going in to the liver through the Oporto hepatis is the Apothic artery proper and the portal vein okay the one that's coming out of the porta hepatis is the bile duct specifically it's gonna be the common hepatic duct okay now here's the next thing I want you to understand these aren't the only things that are going through that Oporto paths we talked very very briefly and we said that there's also going to be a nerve plexus okay that's coming in to the liver and if you remember we called it the hepatic plexus okay so it's gonna actually come in to the liver as well so what is this plexus here called they call it the hepatic plexus and the apat eclectus is really important because if you remember the apat plexus is actually made up of sympathetic and parasympathetic nerve fibers the sympathetic nerve fibers of the appellate plexus is coming from the celiac ganglia and then the parasympathetic fibers is coming from the vagus nerve if you guys remember that so again that's going to be another nerve pathway last one and that's actually going to be draining the liver so there's actually three structures going into the liver two structures coming out of the liver and this last one here is actually called your lymphatic vessels so one more that's actually coming out of the liver here is actually called your lymphatic vessels these are important because they're draining the interstitial fluid and that's important to be able to make sure that that interstitial fluid any of the fluid that leaked out of the capillaries these sinusoidal capillaries is returned back to the circulation that's the significance of the lymphatics so this lymphatic vessel so these are gonna be our lymphatics if you guys really want to know we'll talk about it more in the lymphatic system but these lymphatics from the liver will actually drain into a specific nodes like specific lymph nodes and these are gonna be like your silly act lymph nodes okay so they'll drain into this silly act lymph nodes so now there's an important thing that we should understand all of these things via patek plexus the paddock artery proper the portal vein the bile duct and the lymphatics that are gonna drain to your silly act lymph nodes all of this structure that we consider to be here I'm going to kind of like encase it like this let's do it like that that whole thing right there we actually call that a specific thing and we call that the portal tract okay so it's important to know and remember three things are going into the liver via the portal baddest hepatic plexus about a garden proper portal vein two things are draining it bile duct and the lymphatics okay now one more thing that I want to do here before I keep going on and I just want to talk about oh very very quickly is if you guys remember the liver is actually we talked about this in the development video the liver is what's called intraperitoneal it's an intra peritoneal organ what does that mean that means that if you look at the liver let's say here's the liver okay and here's your falciform ligament right there if you look at the liver it has a tissue that's actually covering its surface for the most part and we call that we call it the viscera peritoneum right we call it the visceral peritoneum now the visceral peritoneum is then going to be connected to the parietal peritoneum so now we're gonna have another one which is gonna be kind of lining the wall and let's just put it like this right here just like this for right now here is going to be the parietal peritoneum okay so now we're gonna have this right here which is gonna be called the parietal peritoneum okay the liver is held inside of this peritoneal cavity by different types of Mezen Terry's like the lesser omentum or the falciform ligament or the other different ligaments that it has associated with it but now one more thing that I want you guys to understand we know that it's actually going to be an intraperitoneal intraperitoneal organ therefore it has a mesentery and it's covered by this mesothelial type of tissue but one more thing the liver has a connective tissue that's covering it okay so it has this connective tissue that's actually covering it and that's important there's a connective tissue covering it and that connective tissue that covers the liver is called glistens capsule the reason why I want to let you guys know this is that glistens capsule is important because it's a connective tissue and it's actually under innervation neural innervation particularly from the intercostal nerves so it has innervation by the intercostal nerves why is that significance when we talk about the nerve supply to the liver there's not just the apat ik plexus but there's also the intercostal nerve supplying the glistens capsule reason why is let's say for whatever reason the liver is inflamed it's starting to distend if it descends it can activate the intercostal nerves in the glistens capsule which can cause us to feel or sense pain so that's important it's an important concept there is that whenever there is the distension of the actual glistens caps or distension of the liver due to hepatitis cirrhosis whatever it might be whatever the underlying etiology is it can activate these intercostal nerves and that could is important because it can actually relay the pain aspect of it okay all right cool so I think we down a perfect a perfect groundwork for that so now what I'm gonna do is I'm gonna take this liver lobule and we're just gonna zoom in on it and we're gonna talk about all the structures associated with it okay so first things first let's talk about these three structures that you see on each end of this hexagon okay on this liver lobule if you will okay so this is our liver lobule our liver lobule and again why is it important because the liver lobule is the structural and the functional unit of the liver okay now what are these three things we already talked about a lot of detail already remember this artery the arterial the Apothic artery proper the a patek artery proper will branch out and to the right left of patek arteries and then into the arterioles those arterioles will go to these liver lobules so what is this right here called this right here is going to be the hepatic not heap a patek artery this is going to be in a patek arterial okay so that's a hepatic arterial and then if you look over here guess what this is going to be that's going to be a tributary of the portal vein so then this is going to be a portal venule okay which is going to be a tributary of the hepatic portal vein what again that branches onto the different parts of the liver and then the other one is going to be your bile duct okay it's going to be the bile duct and again what you're going to notice is that these three structures are located on every point of this hexagonal structure now when you look under a microscope you're gonna see these structures okay and it has a particularly name if you will these particular structures have IDE encased these guys like this have a particular name and this name is called the portal triad okay it's called the portal triad now the reason why I say that is because what else did I tell you was technically at that area well there's also going to be neural innervation and there's going to be lymphatics you can't see this next one I'm gonna put it outside of it just for the sake of this situation here but this is there and what was that that is gonna be a lymphatic vessel so this is going to be a lymphatic vessel so now here's why this is important let's say that if I were to actually understand under histological I can't really see the lymphatic vessels when I'm looking under the microscope but I should know that this structure is still there now I call this entire structure the portal tetrad okay so make sure you understand that there is technically a portal tetrad but again when you look under a microscope it's super super hard to see the lymphatic vessels because they're blind in but they're very very tiny so we generally call this the portal triad okay but do realize there's lymphatic vessels there now next thing that we should understand is we know what's at these portal triads next thing I want you guys to remember is we said that the arteriole and the van you are dropping things off to the liver and the bile duct and lymphatics are draining it let's see exactly how the apat Akkar tear in the portal vein Yale is doing that at each end you're going to see this like read this kind of maroon structure here this varun structure here I'm going to kind of put a little lumen here inside of it I'm gonna have a little little lumen here and that right there is the lumen by which guess what the hepatic arterial is gonna drop its blood off into and guess what else the portal venule is gonna drop its blood into this and now we're gonna have a mixture of what the apat ik arterial blood which is going to be oxygen-rich blood and we'll have a mixture of the actual portal venule blood which is going to be nutrient-rich might be rich in bacterial pathogens of different types right but that's the significance that I want you guys to understand and what's gonna happen is this blood is gonna move Sintra pili right it's gonna move towards the center where this blue structure is and this is gonna happen from each edge so if you were to imagine it would actually drain here move towards that central vein they would both drain into this sinus so capillary move towards this one and then same vice-versa for all them okay now because this blood is mixing and it's moving towards this vein in the center we call this vein right here smack-dab in the middle of this liver lobule we call it the central vein now the central vein is important because the central veins from these different liver lobules will come together so if you imagine for a second let's do it like this let's say for just a quick second let's say here I have a central vein of a liver lobule okay right here so there's that central vein I have another central vein that one comes up these central veins can connect together and form another structure so these are this is my central cv4 central vein then they're going to come together and they're gonna form what's called an inter lobular vein and then those inter lobular veins will eventually come together multiple of them and it will form eventually your hepatic veins and then the apat acquaintance will empty into the inferior vena cava so I just want you to understand the relationship of this okay so these guys are dropping off blood into these sinusoidal capillaries these little maroon things here and the blood is mixing and moving towards the central vein realize that from these central veins a bunch of them can come together and form inter lobular veins which can come together in forma patek veins and then a patek veins can come together and empty into the inferior vena cable so that blood is going somewhere okay it's not just going there and stopping all right so now I've already mentioned this about a couple times what are these maroon structures that I said these maroon structures I'm this one here this one here they're there all these guys they're specialized capillaries that we talked about in the cardiovascular system videos and these are called they just denote them as sinusoidal sinusoidal types of capillaries there's three types of capillaries if you guys remember there's continuous there's fenestrated and then there's sinusoidal capillaries out of those the most permeable is the sinusoidal Kappa Liz if you're remember we said that they have a lot of fenestrations little pores inside of the endothelial cells and they have large intercellular cleft which allows for a lot of macromolecules and plasma and solutes to move in and out of the blood vessel and into the interstitial spaces that's important and if you remember we said the sinusoidal capillaries can be found in very specific places in the body three of those important places if we said is the liver the red bone marrow in the spleen and the reason why I sign these sort of capillaries are really good at trapping old age and defective red blood cells and that's important because you're gonna see some special cells in these sinusoids called kupffer cells that play an important role in that red blood cell degradation all right so that's good enough right now so what do we know we know that these guys are dropping blood up into the sinusoids and the sinusoids are taking the blood towards the central vein okay that's good for right now let's do the next thing the bile ducts the bile ducts are really really cooled because they're picking up bile that are coming in between these actual hepatocyte so you see these cells here these black cells they're the ones that make up about 80% of the liver parenchymal the liver cells right it's actually gonna be your hepato sites these your liver cells and this makes up 80% 80% of the liver parenchymal okay that's that's insane okay there's other cells that we'll talk about - a part of the reticulo-endothelial system like the kupffer cells will talk about stellate cells but these are the most abundant they make up most of the liver and these are the ones that were gonna focus on in the next video okay in between these guys generally in between their apical membranes and we'll zoom in on and after I just want to get the basic thing here is in between them you can kind of see this green stuff that's called bile the bile is actually secreted in between the apical membranes of these goes where the hepatocyte sar juxtaposed there's a little apical membrane which fuses but it forms a little small structure called a bow canaliculus and what happens is the bow can I lick you lie come through these apat asides downs between their apical membranes and then empty and drain into that bile duct okay so now what are these green things here called again and we'll zoom in on Alette later but they're called your bio or your biliary canal lick you lie okay now lick you lie okay and we'll talk about those a little bit later but now we understand that then there's one other area and again we'll zoom on that after but you look here okay there's the sinusoidal capillaries I'm gonna highlight this in orange in between the sinusoidal capillaries and these are parasites you're gonna see this space okay if you guys can see that that's called the signee peri sinusoidal space or another space that we're going to talk about called the space of dis e any of the fluid that's being exchanged between these sinusoidal capillaries we can't just let it sit in that tissue space okay we have to drain it so guess what that can drain into these lymphatics so the next one that I want you to understand is in between these sinusoidal capillaries right here is a nice little space and what is that space they're called that space is called the space of dizzy okay so we'll call this one the space of dis e or the peri sinusoidal space okay so now we have covered a big chunk of this liver lobule now so now what I want to do is so that we can really really understand and even zoom in on some other structures that make up the liver lobule is what I'm gonna do is imagine here is this sinusoidal capillary and here's some hepatocyte s'right here okay and then here's the portal triad I'm gonna take that chunk right there and blow it up okay and we're gonna look at it okay so now we're zooming in on it right so just do a little bit of orientation again this right here you guys already know what this is is their central vein okay so this is gonna be our central vein and again if you guys remember they come together interlab Euler veins and two Labradorians come together make a patek veins a patek veins empty into the inferior vena cava which drains the liver and takes it up to the right atrium as we know other things hey you guys should understand before we really get into this because these little red structures here these little cells that are making up this capillary again what is this capillary here called it is called a sign you soil capillary and again just to review what are the three places you can find the sinusoidal capillary you can find it obviously in the liver you can find it in the spleen and you can find it in the red bone marrow and why is it so special if you guys remember we said that it's really good at trapping old-age and defective red blood cells that have reached their prime it oh they've reached the end of their prime right at 100 120 days okay so that's our sinusoids then if we look we have this space in here what is this space it's that orange space if I were to kind of highlight it a little bit in here write all this right here that we kind of highlight over there as orange which is drained by the lymphatics this right here is called the space of dissy right or the peri sinusoidal space and then the next thing is just to review this this is our actual bile duct this right here this green structure is going to be called the bile can now lick you lie and then we have this structure here which is going to be our portal vein which is a tributary out so this our portal venue so portal venue and then we got this bad boy up here which is going to be the actual hepatic arterial so this is our hepatic arterial and remember this guy is giving the oxygen-rich blood and putting that into these actual sinus or the capillaries two more structures that we get to finish off and then we can really dive into this is gonna be this guy this guy's so darn cool he is called our kupffer cells okay these are called kupffer cells they're macrophages they're a part of the reticulo-endothelial system they make up a large large portion of it another one is going to be these like special brown cells here they'd be here they're found inside like for example here's another one this guy right here is called your hepatic stellate cells they have two names you can call them stellate cells or another name that they have in textbooks is called the I toast cells okay they're really really interesting cells and we'll talk about them too all right so now last thing is we have these black cells and these black cells are our hepatocyte s' okay all right so now the blood if you remember from the portal venule is moving into this actual sinusoid capillary and the blood from the soap at ik arteriole is emptying into the sinusoidal capillary and it's moving right centripetal as it's moving towards the actual central vein we know that there's substances that are going to be in this portal vein you blood and substances in this hepatic arterial that these are parasites are going to utilize for example if we were to zoom in on the blood flow going through there you're gonna have some red blood cells all right so let's say here is your red blood cell in your red blood cell you're gonna have a special special protein which is called hemoglobin and he's gonna be in the oxy form HBO - we know that this is a systemic arterial blood so the percentage of this oxyhemoglobin is like 98% it's really really saturated with the oxygen what do we know we know that this hemoglobin is gonna let go of this oxygen and it's gonna deliver the oxygen to these tissue cells because these hepatocyte smen they are hard core they perform a lot of functions and they're unbelievable all right so these guys are really important so the hemoglobin is gonna be dropped off to these tissue cells because your tissue cells you know they're gonna be producing a lot of co2 co2 when combined with water makes carbonic acid and then that breaks down right so if we know this you know your tissue cells are making a lot of co2 combined with water they make carbonic acid combined with that they make what's called co2 sorry they make what's called bicarbonate so bicarbonate and they make what's called protons and we know that the protons are important because they bind onto hemoglobin triggering the Bohr effect to let go of the oxygen same thing is we know a lot of the co2 will actually bind on to hemoglobin inform the carb I mean the hemoglobin and again that'll all support to dropping off the oxygen to the tissue cells so we know his significance is dropping off oxygen to the tissue cells the portal vein yyl he is delivering a lot of blood that's rich in nutrients so this is going to be tons and tons and tons of nutrients so if you remember and we'll talk about this more and we get into the apat aside video we're gonna have a function of it a lot of these nutrients are gonna be taken up by these of potus i'ts and use for various purposes and we'll talk about that but here's what I wanted to talk about other things that are unfortunately in the blood when we ingest food and sometimes it can actually come from our actual intestinal lumen is bacteria so let's make bacteria let's make it this blue color here so let's say here we have this bacteria this bacteria is not supposed to be here we don't want it there it's there we do not want this to continue to just funnel right past these sinusoidal capillaries going to the central vein and then get into our systemic circulation that's bad all right because bacteremia if in high high levels can cause septicemia so we don't want that we want to make sure that this bacteria is taken care of and we fix it before it leaves and goes into the systemic circulation so cover cells are your be thankful for them because they stop it right there so one of the best things about these copper cells their macrophages what do you guys know about macrophages they're phagocytes so they love to engulf particle matter so what would they do they'll actually form these those little pseudopods right if you guys remember what you guys watched our immune system videos they'll form those like little pseudopods and it'll ingest that actual bacteria it'll take it in and gulf it and if you remember if we take it inside so let's say that we actually phagocytose it internalizes this actual bacteria takes it inside and it puts it into what's called a phagosome okay so if your remember here we'll have like a little vesicle in there and that vesicle will have the bacteria well from this it can do a bunch of different things they can combine it with lysosomes right so we could take this and combine it with special organelles that are present inside of this actual cutpurse l-like lysosomes when these two fuse they form what's called a a lysosome and what does that mean that means I can take this bacteria okay and I can start breaking it down because what's gonna happen is the lysozymes contain very very powerful hydrolytic enzymes that'll start destroying this bacteria and so it's gonna break down this bacteria pretty darn good okay so that's one of the beautiful things about these kupffer cells is that they have the ability to perform phagocytosis and they have very very strong lysosomal enzymes so these lysosomal enzymes have the ability to completely break down the bacteria all right super super important other things that the cup for cells function to do is not just responding to bacteria these things are at least I'm telling you these things are awesome they can also respond to particular types of toxins there's special things in bacteria and like gram-negative bacteria of gram positive and gram negative gram-negative bacteria have a special thing on their outer membrane which are called lipopolysaccharides okay these lipopolysaccharides can interact with these kupffer cells one oh hell i'll show you how i come down here for a second here i'm gonna have a cup for cell let's say here's a cover so okay there's my cup for cell hey I'll draw its little nucleus there okay and then what happens is on its membrane it has particular proteins like these protein subunits here and these proteins are very very specific we talked about this again in our actual immune system video but this is called toll-like receptor type 4 and this toll-like receptor 4 is usually coupled with another protein and this protein is called cd14 so they call this one CD 14 what happens is these toll-like receptors have the ability to identify or bind with these actual endotoxins and what is endotoxins here called it is called lipopolysaccharides what it can do is it can send signals to the actual Kupfer cell's nucleus and then the cup for cell will start synthesizing a lot of proteins right you know that'll go and trance transcribe the actual DNA to our mRNA and then MRO and our mRNA will get translated into various types of proteins right and then what happens some of these proteins that it might release are gonna control a bunch of different functions for example some of these proteins might stimulate specific pathways so specific here let's say specific pathways and it might trigger the release of a bunch of inflammatory cytokines so it could cause the massive release of a bunch of inflammatory cytokines for example just to name a few it can release what's called tumor and a chronic factor alpha it can release interleukin 1 interleukin 6 oh this one is a big one reactive oxygen species that is a huge one it has the ability to generate a tons of reactive oxygen species and it also has the ability to release other chemicals like transforming growth factor beta nitric oxide and different types of prostaglandins we can throw that last one in there prostaglandins a bunch of different chemicals but all of these are inflammatory cytokines and they try to enhance the inflammatory response so that's really really interesting they also have the ability to interact with parasites so they can also break down parasites so certain types of parasites it has the ability it has special receptors on it that recognize these actual parasites okay and the last thing that is really really important for these kupffer cells is they have the ability to break down old and affected defective red blood cells so for example I have another cup for sale here here's another cup for so if you guys remember we said that the red blood cells have you know about 120 days lifespan right and as they get older remember there's a protein called spectrin and an iron that controlled that's actual flexibility and pliability but as the red blood cell gets older it loses that pliability and if you remember there is a very important component inside of this actual red blood cell called hemoglobin so let's say that this red blood cell is greater than a hundred to 120 days okay so it's bye-bye time this actual cup four cell has special enzymes in it that have the ability to break down the hemoglobin okay and what it can do is it can break down the hemoglobin to its two components one is called heme and the other one is called globin globin is a protein so what the globin will do is there's going to be special enzymes that will break down the globin into amino acids but then guess what we have another component inside of this cup for cell it has another special enzyme that can break down the heme into what's called Billy Ruben eventually it goes to Billy Verdun and then Billy Verdun to Billy Ruben I'm not gonna spend too much time when I just want you to know that it actually is broken down into Billy Ruben okay and one other component of the heme is you release what's called iron and iron you know can actually be bound to specific proteins inside of the cell which is called a Bo ferritin and then what it combines with the iron deforms ferritin or we can put it into the blood and combine with transfer and we've already talked about this many times right but the significance here is that Billy Ruben we can push it out of this cell and guess where that actual bilirubin can go for example let's say that it breaks down the red blood cell right there and it pushes out this substance called Billy Ruben that Billy Ruben is actually going to be taken up their special transporters located on the actual basolateral cell membrane of this hepatocyte that can take the bilirubin up and they can conjugate it we'll talk about that in the biliary system video but then that Billy Rubin that we actually get inside of the cell we can push it into the actual biliary canal lick you lie and then guess what if we push it into the biliary can I lick it I guess what will happen it'll go into the bile duct as an important component of bile okay so that's important Billy Rubin is an important component of our bio okay so what have we understood so far we know the portal vein Y we know what it's doing we know the apat ik arteriole we know what kind of capillaries are coming through here we know the general functions of this cup for cell okay this is just general ones controls phagocytosis of bacteria it can actually recognize foreign parasites it can react with different toxins like lipopolysaccharides and it can actually break down old and defective red blood cells and it also has an important function with controlling what's called immuno tolerance okay in other words it can actually inhibit specific cd8 cells or cytotoxic T cells from completely unknowing undergoing specific immunological reactions inside of this tissue okay that's important all right one last cell that I want to talk about here is this guy right here this orange so we said Stehly cells they have a particular function to that particular function of these stellate cells is they are what's called they store vitamin A okay so they store vitamin A and some fat so they can store what's called vitamin A now these cells are pretty much quiescent in other words they don't really have any specific functions they don't really do anything crazy they just are responsible for storing some vitamin A and some fat but if over time there is consistent let's say bacteria or parasites or alcoholic induced damage to the liver or hepatitis or rare diseases like Wilson's and hemochromatosis whatever it might be the liver undergoes consistent damage and inflammation what will happen is due to that these stellate cells can become activated and what they can do it so let's say here I have a stellate cell okay they're generally pretty much quiet all right so they're pretty much in just like a resting phase they're not really doing anything but if for whatever reason you continue to cause this stellate cell to have a lot of tissue injury so there's this excessive tissue injury okay over time again like hepatitis cirrhosis you know maybe due to hemochromatosis Wilson's disease infections whatever it might be it can convert these Stelly cells into these special cells and these cells are responsible there for producing a lot of what's called collagen type 1 so these are called Myo fibro blasts so the satellite cells can become my own fibroblast and produce a lot of collagen type 1 you know why that's important because if I start producing a lot of collagen type 1 in this area guess what it's going to do to the blood vessels it's gonna cause the blood vessels to become really fibrotic if the blood vessels become very very fibrotic it can narrow the blood vessel walls and then the blood trying to come through that area is going to be impeded guess what the Bloods gonna backflow and if it back flows and back flows and back flows guess so it can produce portal hypertension so that's important because these Stehly cells are responsible they're one of the main culprits of causing this fibrosis of the liver due to consistent in chronic tissue injury all right cool that's that guy now next thing I need to talk about here you have your pata sites right we've talked about all these parts here one more thing I have to talk about is these actual apat a sites these are pata sites are so darn cool we're going to look at their function later but for right now we have to talk about this last thing which is the bio duct the actual pata sites are responsible for making bile and if here's what I want you guys remember if you don't remember anything else about bile just please remember the three main components of bile one is your bile salts or your bile acids okay so biles bio connection bile salts can come in three different ways they can be a bile salt there gonna be a bile acid they can be what's called a conjugated bile salt we'll talk about that when you get to the biliary system and this is like kolak acid chino deoxycholic acid and it can combine what taurine and glycine and stuff like that another component this is like 70% of it this is the most important one another one is called phospholipids or lecithin this is another really important component and then another important component is called bilirubin this is what causes the pigmentation in the bile and there's other components in a tube but these are the big big ones also cholesterol the liver cells the apat aside are responsible for making that bile so on one side look at this cell it's so cool it's got like a double side itself double sided grape one side faces the actual sinus sort of capillaries and again this is called the space of disi here's what's odd this side has micro villi okay if you look at this what are these like little things here called these are called micro villi they're responsible for increasing the surface area of these liver cells okay super super important cells are responsible for increasing the surface area this side where the micro villi is like imagine here I take a cell here's a here's a pata site on one side it has the micro villi this side it's Zoe this is the basal lateral membrane that's what's so odd about this it's on the opposite side usually the basolateral membrane will be this side but it's different right for the actual liver so in this on this side is where the actual capillary system is on the other side is the actual biliary canaliculi and this side right here facing that is called your apical membrane that's pretty weird because it's kind of opposite of what you would normally think usually we think the apical membrane is going to be towards the sinus or the capillaries in the basolateral toward the bile canaliculi but it's not one other thing I want to make sure I clarify here is when you look at these apat asides really the bow cannot lick you lie it's actually formed by these two up at a site so imagine he rabbit up at a site and I kind of make like a little like thing like this and a little thing like this you see how they're two connected they're actually connected by important structures three important structures actually make up the apat aside connections tight junctions desmosomes and even some gap junctions okay but there's this tiny little structure between the two juxtaposed cells when they're apical membranes fuse it forms these little canal liq you lie and that's called the biliary canaliculi so really what happens is in between these of parasites they're actually taking all the bile and secreting it into this but it's easier to show it like this all right when we're looking at in a functional diagram so really understand that the bow can I lick you lie is actually formed by two juxtaposed hepatocyte s' their apical membranes are fused but it forms this tiny little groove or tiny little space called the biliary canaliculus all right and then again what happens to this bile the bile is going to move through this biliary canaliculus system and then move out and into the bile duct and then if you remember the comma the bile ducts will become your left and right a paddock ducts those will form the common paddock ducts they'll fuse with the cystic duct of the gallbladder and form the common bile duct which will go down and fuse with the main pancreatic doctor all right so one last thing before we look at the different types of liver lobules as we said we have this space called the space of dissy right and this is where a lot of the exchange between the plasma of the sinusoidal capillaries and the interaction between the apat asides alright so you know that a pata sites they could be putting secreting different things and that could be moving into the blood or there could be solutes coming from the actual blood and moving to the passage but there's this exchange one last thing is we said that the basolateral membrane is the microvilli right it's where the micro villi are what's really interesting is that there's a lot of connective tissue in this area in the space of dizzy a lot of connective tissue so you can say that the apat asite s-- they rest on this connective tissue matrix in the space of dizzy and this connective tissue matrix is made up of a ton of different types of collagen okay for example it could be made of collagen one it could be made up of collagen 4 it could be made up of collagen 5 it could be made up of collagen type 6 whatever there's a lot of other proteins too there's fibronectin undulant proteoglycans so many different structures but the significance is is to remember there's like this connective tissue bed that the basolateral membrane of the apat asides rest on kind of like a basement membrane in a way which is really interesting okay so now we've really really dived into this actual liver lobule I think now we can safely talk about the three different forms of liver lobules at this last part over here okay so last thing we got to talk about here guys is there's three different ways of looking at a liberal objects we look at a liver lobule in pretty good detail alright we talked a lot about it but there's ways that you can kind of like functionally classify these liver lobules so let me write that down here for you there's three ways okay so one way that we're gonna look at is we're gonna look at what's called the classic liver lobule okay the classic liver lobule and that's the one that we kind of focused on primarily over there another kind is what's referred to as the portal lobule and then the last one which is my personal favorite is the a sinner lobule or the Ascenta slob you'll hear let's do it like that a cinema snob you'll okay so these are just different ways of looking at the liver lobule and functional way in a functional way okay so let me explain first off the classical one but that's the easy one this one is referring to the blood flow okay this one is referring to the blood flow so it's looking at the blood flow of two vessels okay via Patek arterial and the portal venule it's looking at the how that blood is flowing from these guides toward the central vein okay so it's looking at the blood flow of the apat Akkar tear and the portal vein Ewell to the central vein so when we talk about this way for example what does this mean okay here's your portal triad here's your central vein from this the blood but from the a patek arterial and the Apothic venule is moving in a direction toward the central vein so to simplify it in one arrow this blood will be flowing from the portal triad towards the actual central vein portal triad central vein portal triad to central vein and vice versa so the big big significance here when you're looking at a classic liver lobule as you're looking at the blood flow coming from the portal triad to the central vein the next one is the portal lobule and the portal lobule is referring to the actual direction of the biliary flow okay so it's looking at the direction of the bile flow so what do I mean if you look here you have to kind of make this a three wave structure so here I'm gonna kind of go I'm gonna connect this central vein and this central vein in this central vein all together in one so I'm gonna come here to this go to this and go to this so what you do is you make like this triangle now in the center of the triangle it should tell you that is going to be where the actual bile duct is so now from each one of these central veins follow the flow of bile towards the to try it so now look the bile will be flowing this way the Bible will be flowing this way and the power will be flowing this way and in the center is where you should find your bile duct okay that's the significance of this portal lobule is that the portal lobule tells us the direction of the flow of bile moving from the central vein towards the actual portal triad okay that's that one the last one my personal favorite here is the ascend our lobule and this tells you the flow of arterial blood so this is going to tell you the flow of oxygen rich blood so this one is really darn cool so what I'm gonna do is let me do this one in black what I have to do is I have to take from this central vein okay I'm gonna go to that point of the lobule then from that I'm gonna go to this point of lobule and I'm gonna do the same thing over here I'm gonna work to this point and I'm gonna work to this point now if you guys remember there should be blood moving from the apat ik arteriole and moving towards the central vein right so for example we'll be going like this and it would be going like this so the blood is moving from this actual portal triad and moving towards the central vein it creates what's called this zoning so now what I'm going to do is I'm going to come down with the baby blue and I'm gonna zone off each area so this zone right here this zone right there and I'm gonna come back over here and I'll have this zone right here that one that one and that one so now look what I form I kind of form like this rhomboid like structure here each one of these is an individual's own so for example this will be Zone one the one closest or what's called Perry portal so the apat asides in this area is going to be perry portal they're close to or next to the portal triad then we're going to go in the center of this one and that's going to be Zone two and as you know now the one that's closest to the central vein is going to be zone three okay so this is called the Ascenta smaadahl or the Ascenta slob you'll is that you're looking at the flow of blood the flow of oxygen-rich blood from the portal triad towards the central vein and again the apat asides in this area are referred to as perry portal these are just going to be the ones between and this is gonna be called perry vin euler ok perry vin euler hepatocyte s-- why did I mention this here's what's cool about this one and each zone ok for example let's say I have zone 1 particularly in zone 3 zone 2 is the intermediate between so we're not going to focus a lot on that we're just going to say that it does a mixture of functions between these two zones zone 1 if you think about it it's closest to the apat Akkar Tyrael so it's going to get the highest it's gonna get the blood that's richest in the amount of oxygen first so as the blood is coming through it's gonna have a lot of oxygen it's flowing through i'm gonna give off oxygen to this cell and this cell in this so i'm gonna keep going give off oxygen to this cell this song keep going by the time the blood gets from the actual portal triad all the way towards the central vein what do you expect the partial pressure of oxygen to be at that point lower so the partial pressure of oxygen in zone 1 we expect to be the highest and the partial pressure of oxygen in zone 2 we expect to be the lowest so why is that important zone 1 is going to be the most resistant to any type of circulatory compromise if for any reason your blood is you have a decrease in blood volume like hypovolemic shock or whatever this zone is gonna be their most resistant because it's going to get the most oxygen from the actual arterial the because it's the first one there whereas zone 3 is going to get the least amount of oxygen so there's gonna be most necrosis or most death or most ischemia to the cells around the central vein that's important another the reason why this is important is because each one of these zones perform different functions that's so that's one of the coolest things ever because they call it zonal heterogeneity hetero Genuity what that means is each zone performs a specific metabolic function what I mean for example zone one its highest in oxygen so it's gonna want to perform oxidative metabolize so for example in zone one it's gonna have the most oxygen so you want to perform a lot of oxidative metabolism for example some of the pathways that you'd want it to be is like amino acid metabolism that could be one pathway there that's a metabolic pathway that requires the presence of oxygen other ones could be gluconeogenesis that one is also an oxidative pathway that requires again it's going to require oxygen ATP other ones would be like cholesterol synthesis cholesterol synthesis bile salt synthesis urea Genesis so you're really cold so that your region assists things like that it's gonna be performing a lot of these pathways another one is it performed beta oxidation so you know you have another one there which is called beta oxidation the whole point I want you guys to understand is is that if you look at the mRNA that's expressed in zone one it's gonna be different for the particular enzymes that function primarily in that zone whereas if you look at and zone three the mRNA it might be more specific to different pathways that's what's so cool they actually did Studies in zone 3 has the highest mRNA expression of an enzyme called glutamine synthetase so what do you think that means that means glutamine synthesis going to occur most in zone 3 that's the significance here so this one is going to perform many more pathways like this would perform glycolysis because it's not going to get a lot of oxygen obviously it'll perform things like fatty acid synthesis it'll perform things like ketogenesis again it'll perform what's called glutamine synthesis another really important one that we're going to talk about in the PATA site video is it performs what's called we'll call biotransformation or Zeno biotic metabolism and that's basically metabolizing different types of toxins and drugs and whether they be endogenous or exogenous compounds so that's really really important to understand okay so three different ways that we can functionally classify these liver lodges is classic which is just saying the blood flow going from the portal triad towards the actual central vein both the mixture of hepatic are two important venule blood the portal lobule which gives us the direction of the biliary flow which is gonna be if we can look at it in this triangular like way it's gonna be flowing from towards the from the central vein towards the portal triad and the last one is the center lobule which is making this rhomboid like structure and it's separating the apat asides into three zones zone 1 zone 2 and zone 3 zone 1 highest resistance to circulatory conference cuz it's gonna get the most oxygen zone 3 it's unfortunate gonna be the one who might have the most necrosis and ischemia and cell death and because it's not getting a lot of oxygen zone 3 will perform pathways like glycolysis fatty acid synthesis ketogenesis glutamine synthesis xenobiotic metabolism where a zone number 1 might be more for amino acid metabolism gluconeogenesis cholesterol synthesis biosynthesis the urea genesis other different pathways and again that should make sense because different areas have this thing called zonal heterogeneity i engineers in this video we talked a lot about the astrology of the liver I really do hope it made sense I know it was long and I thank you guys for sticking in there and I hope that you guys really did learn a lot and I really hope it made sense I truly truly do on that it really is our goal here at an engineered science and we're dedicated to that goal if you guys did like this video please hit that like button comment on the comments section and please subscribe also if you guys get a chance go check out our Facebook or Instagram maybe even our patreon account if you guys had the opportunity to donate me to even $1.00 it would make the prints we appreciate you guys and as always engineers until next time [Music] you [Music]