The cells of the liver

Hello, everyone. In this video, we’re going to move from the gross anatomy of the liver to learn more about the key cells which live inside to understand how they contribute to making your liver work. We will refer to cells in pictures which we mentioned in our “Liver Under the Microscope” video that we filmed with Professor Hubscher. So feel free to have a look back at that again to remind you of how this tissue is organised. This image shows you how the normal liver looks under the microscope. You can see that most of it is made up from our first pink cell type– the hepatocyte.

But before we get on to this, I need to describe a couple of general cell types so that you can understand what comes next. They’re illustrated in this picture.

Our first important cell type is an epithelial or barrier cell. These line surfaces that are exposed to the outside, like your lungs and skin. And they can protect organs and absorb materials like nutrients in the gut. They can also secrete materials like sweat from the skin. And there are several types of epithelium in the liver, which we’ll come on to in a minute. Our next important cells are endothelium. These are the thin, pale pink cells in this image. They’re another barrier cell population which line blood vessels, and they can control blood flow and clotting and also restrict the traffic of materials to and from an organ. And they tend to allow white blood cells to fight infection.

So we should mention these white blood cells themselves. We tend to think of these as being located only in the blood, and they do indeed move around this way. But they actually tend to do their job to fight infection inside tissue. So even normal tissue has some blood cells inside, for this will increase during inflammation or infection. So let’s look at the liver now. Here’s our image of the normal liver again. And let’s start with those hepatocytes– the cells that make up most of this pink material that you can see here.

These are epithelial cells. And they make up about 80% of the volume of the liver, with about 300 billion cells in total. They’re 20 to 40 micrometres across, which is about half the thickness of one of your hairs. And they live for quite a long time– about six months– and tend to divide quite slowly. You can think of them as the power station of the liver, because we’ve already mentioned how they can make bile, store vitamins and fats, make important proteins, secrete glucose, and are also involved in detoxification and metabolism.

Our next cells are another epithelial population, this time, the biliary epithelial cells, which make up about 1% to 3% of your liver tissue. These cells are labelled with the arrows in the images shown here. They look a little bit like a string of beads. They make up the biliary channels or bile ducts, which can range in size from tiny little structures of the portal areas to great big tubes which drain out into your gall bladder and are shown in green in the bottom image. These are another quite slow-growing population which transform materials to and from the bile– things like water and bile salts for recycling.

They are the target of some autoimmune liver diseases, which we will hear about next week. And incidentally, these bile ducts are also the site of resident liver stem cell populations, which can help repair the liver if the hepatocytes are really badly damaged.

There are also endothelial cells in the liver, indicated with the arrow on the left picture and the brown staining in the right image. There are several different kinds of endothelium in the liver which range from capillary-like cells between the hepatocytes, to the great big cells in the portal areas like the ones on the left. The capillary or sinusoidal cells, in particular, are really good at scavenging and recycling material from the bloodstream. And all liver endothelium are involved in the regulation of inflammation. So let’s look at those white cells next. Even in a normal liver, some of these are present.

And they sit around those areas where the blood comes into the tissue, indicated by the small blue dots labelled with the arrow in the top figure. So toxins or bacterial viruses from the gut or the rest of your body can enter here. So it makes sense to have white blood cells nearby to deal with any problems. There are several different white blood cell types which can either engulf or eat pathogens like bacteria to kill them. They can kill infected or tumour cells. Or they can secrete compounds, which direct other cell populations to remove the problem. In disease, the number of white cells increases rapidly to fight infection with something like a hepatitive virus.

And you can see this in the bottom picture where there are lots of those blue dots. And the term “hepatitis” actually means “inflammation of the liver,” where you have lots of these white cells and tissues like the picture here. They generally do a good job. But in chronic disease, the white blood cells can become overstimulated, and they actually begin to damage tissue. So this ability to either do good, in terms of removing viruses and bacteria or tumours, or to do bad, in terms of causing collateral damage to tissue, means that targeting white blood cells is a good way to modify liver disease.

Next, we move on to some cells with a bit of a dual personality. These are the stellate cells, which are labelled “HSC” in this image. They’re star-shaped cells, hence the name, which sit between hepatocytes and endothelium like the filling in a sandwich. In health, they grow slowly and are important for storing useful fats or retinoids like vitamin A, which are used to regulate liver growth and function. However, in response to liver injury, these cells change dramatically. They lose this retinoid, and they begin to proliferate fast. So they increase in number. Most importantly, they secrete a lot of extracellular matrix proteins. These are compounds like collagens which make up scar tissue, and they contribute enormously to fibrosis.

For this reason, many drug companies are trying to understand whether you can selectively target them in order to reverse fibrosis.

So while we talk about scar tissue, I thought we’d remind you of these images from our discussion with Professor [? Hopshire. ?] If you look at the bottom image of the cirrhotic liver, it graphically shows you this buildup of connective tissue in dark pink. There is some connective tissue and healthy liver made, again, from materials like collagen, which holds together the tissue and forms a scaffold. However, as you can see, when those stellate cells are activated in disease, you get this enormous increase, which compromises the rest of the tissue.

So now, let’s remind ourselves of how these cell types fit together. Please excuse my drawing in this clip. So we’ll start with structures which are called liver lobules. These are the functional units of the liver. And each hexagonal unit here is about a millimetre across.

At the centre of each, is a vessel lined with endothelial cells, which takes the blood out of the liver. And at the corners, are the portal tracts, where blood enters from the hepatic artery and the portal veins, and also where bile– collected from between the hepatocytes– drains into the bile ducts.

Cords of hepatocytes or strings of hepatocytes radiate towards the centre of the lobules like the spokes of a wheel.

So now, if we look closely at one of these cords of hepatocytes, you can see that two rows of hepatocytes are separated by a blood channel. This is like a capillary, and it’s called the sinusoid. So these are these two strings of hepatocytes here.

The stellate cells are dotted on top of these hepatocytes. And they form contacts with both the hepatocyte underneath and the endothelial cells, which sit on top. And I’ll draw these in in a minute.

So this is the endothelium on top.

So blood will flow down this channel, or sinusoid, over the endothelium. And any useful material can pass through these cells to gain access to the hepatocytes.

And also, anything useful which has been made by the hepatocytes– like a blood clotting factor or albumin– can be secreted in the opposite direction into the bloodstream.

So if you superimpose this now back on our bigger picture, the blood is flowing from the edges of the lobule towards the centre, and this maximises exposure of all these cells to the blood.

OK, so that’s the major cells that make up this liver cupboard. And we’ve tried to describe to you how they all fit together. In our next activity, we’ll learn a little bit more about some of the major functions of the liver.