Hepatic Lobule

00:00 And under higher power, you can see components of these hepatic lobules. On the top right-hand side, you can see a central vein, hepatocytes. And the little light colored areas are the enormous networks of sinusoids draining pass those hepatocytes into that central vein. And then on the outsides of these central veins in the corners of the hexagonal hepatic lobule, which you don't really see clearly in the human, you can see components of the portal triad, the hepatic artery, the portal vein, and the bile duct.

00:40 They're very small to identify. Very hard to identify because they're so small in some cases. So look very carefully at the epithelial linings, cuboidal linings to identify the hepatic duct and the endothelium and smooth muscle to identify the hepatic artery. The portal veins, of course, are much larger and easier to recognize. Here is a high magnification showing the hepatocytes bathe with blood through these sinusoids, and the very close opposition of these hepatocytes.

01:17 They have lateral and apical borders that open into a bile canaliculus.

01:21 The sinusoids are separated from the hepatocytes by a space of Disse. That space of Disse is going to have in it some very important ultrastructural details of the hepatocyte such as microvilli that I will describe later in this lecture.

01:39 Now on this slide, there are a number of descriptions of different ways of classifying the hepatic lobule.

01:47 If you look towards the top of the diagram, just recall what the classic hepatic lobule was. At the top are labelled components of the portal triad, that if you remember, sit on the edges of the outskirts of the hexagonal-shaped hepatic lobule. And they contain the bile duct, a branch of the hepatic artery, and a branch of the portal vein. And in the center of the lobule is the central vein that collects the blood that passes along the sinusoids pass to all the hepatocytes. Well, that's the classic lobule. Now, there are two other lobules that relate to slight different interpretations of flow of bile and also the blood supply to the lobule. Number 2 there talks about the portal lobule. That is the lobule that really includes the bile ducts as the center of that lobule, the central components of the lobule. And if you look at the diagram, it shows that this lobule is shaped a bit like a triangle. It includes regions bounded by the central vein at the apex of each of these triangles.

03:14 And so within that triangular space, the bile canaliculi between all the hepatocytes in those three adjacent hepatic lobules all drain into one bile duct in the center of the lobule. Down the bottom is another description. That's the liver acinus. And that's based on the supply of blood to two adjacent hepatic lobules, the classic lobules. And the blood drains from the edge, the lateral border, the shed lateral border of two hepatic lobules. The blood drains from the hepatic arteries bathing that area towards the central veins of two adjacent classical lobules. And so that has a number of implications. It divides the zone from the lateral border, the shed lateral border between two classic hepatic lobules. It divides the zone from that border to the central vein into three. Zone I is representing hepatocytes adjacent to the lateral border. Zone II is towards the middle. And zone III is adjacent to the central vein. Now that, as I said before, has implications functionally. If you go out to a party and have lots of cake, then when all that glucose is circulated from your portal vein to the liver, then the cells that are in the region labelled I there, the hepatocytes in that zone, are the first ones that can ingest or take in all that glucose until they can't take it anymore and they store it. Zone II and III then get the leftover glucose that the zone I cells cannot absorb.

05:21 Zone I cells also get first access to an oxygen-rich blood supply. Zone III is a zone where they get less of that oxygen. The zone I cells do a lot of the work of the liver. They are the ones that create all the plasma proteins and secrete them into the vascular system into the sinusoids until they're then distributed to the rest of the body. As I mentioned before, they store a lot of glucose.

05:52 Zone III are those cells that tend to detoxify substances. So that there are these regional differences in the jobs that the hepatocytes do. Zone I, of course, is going to be more affected by alcohol in the blood and toxins and poisons, whereas, the hepatocytes in zone III are going to escape to some degree the insult from those substances. Zone III do not have enough oxygen sometimes to resist the effect of certain poisons, where zone I does. And so this differential, in certain insults to each of these zones and to certain functional components, is useful to the pathologists when they're diagnosing certain diseases or insults that the liver is exposed to. Here on this slide are two sections through the liver.

06:59 On the left-hand side, you can see a section at low magnification, and right in the center is a portal triad. You can see a branch of the portal vein there and two very tiny little structures which will represent branches of the hepatic artery and the hepatic duct. On the right-hand side, a stain has been used to show macrophages.

07:30 Macrophages sit within the boundaries of the sinusoids. They're called Kupffer cells.

07:35 As I explained in a lecture on connective tissue, macrophages are named different names in various organs.

07:44 And also, I explained in that lecture that they're hard to identify. But sometimes if you inject an animal with a vital dye, and, in this case, a blue dye, and that's taken up by the blood stream, it's then ingested by these macrophages. And then when the animal is sacrificed and then you process the tissue, you can see them as you see here. They have enormous jobs to do. They mop up damaged red blood cells that happened to be around, they mop up debris, macromolecules, etc. The sort of typical job they have in other tissues. There's also another cell type shown there, but you can't really differentiate it from the endothelial cells lining the sinusoids. That's called the ito cell. You know the liver itself can undergo regeneration that can repair itself. Those hepatocytes you can see are often binuclear, but they're quite large as well. They can be 20 by 30 microns in size. They can divide and regenerate. And those ito cells, I mentioned a moment ago, have a role in readjusting the extracellular matrix, and the support structure of these hepatocytes. And they also have a role in initiating and controlling that regeneration process. They're also probably phagocytic to some extent.