So the liver is your largest organ. It’s about a kilo and a half. Sort of three pounds. It’s about the size of a rugby ball, and about 1/50th of your body mass. It grows to fit your size. It’s made up of about 100 billion cells. And it’s your largest solid organ. So if I take out Dave’s lungs here, you can see the liver.
It’s separated into two different lobes, a right and left lobe, separated by this ligament here, the falciform ligament. And it’s closely associated with these other abdominal organs. And actually, if you turn it over, you can see there’s a depression where the kidney and the intestines actually press against the liver. It’s held in place by intra-abdominal pressure, by the diaphragm, and by the peritoneum. And it’s actually protected by a collagenous capsule, which just keeps the surface protected. If I turn the liver around, you can see the point where the blood enters and leaves the liver. And the liver is unusual in that it has a dual blood supply.
So you have oxygenated blood coming in through the hepatic artery, but you also have nutrient-rich blood, which comes directly from the gut, also entering by the portal vein. And then you have the exit where the bile that’s made in the liver actually comes out and enters the gall bladder. So this is the gall bladder here. You can see it’s sitting just underneath the liver at the back. It’s about 10 centimetres long. It’s like a little bag. And it stores about 50 millilitres of bile, which you make throughout the day. And it’s sort of squeezed and secreted into your intestine down here, as you need it when you eat. So it’s stimulated by the presence of food in the gut.
A little sphincter contracts and actually delivers this bile into the bowel where it can help you digest fat. So if we talk about the blood supply again, a little bit more, about 75% of your blood actually comes in via this portal vein. So this is the supply coming in from your intestines. Whereas about 25% of the blood is oxygenated and that’s what’s coming in through the hepatic artery. And the blood then enters through both these routes and mixes within the body of the liver before it actually drains and exits the liver via the inferior vena cava, and goes back up into the systemic circulation.
Now based upon this blood supply and this bile drainage, you can actually divide the liver into anatomical sections. So rather than just this left and right half, you can actually split up into separate segments, each of which has its own bile supply and blood supply. And this is really useful for surgery and treatment of things like tumours, because you can actually take out a portion of the liver, perhaps which has a tumour in it, with its own independent blood supply, and the remainder of the liver isn’t compromised. And we’ll talk about how the liver actually grows back, or regenerates, later on in the course. So I’ve covered the anatomy of the liver now.
But what we need to do next is talk about the microscopic anatomy of the liver. So the way that we would actually look at this is to take a sample of the liver that we can put under the microscope. And this is usually done by a liver biopsy. So what your physician would do is use a needle to actually take a sample. He would go through between the ribs here, and take a sample from this larger right half of the liver, which could then be preserved, put under the microscope. And then we can actually look at the cells and try and work out what’s happening.
So in our next video, we’ll have a conversation with one of the liver pathologists here in Birmingham, Professor Hubscher And we’ll move from looking at the large scale anatomy of the liver to the cellular level, so we can understand a bit more about what the individual cells which make up the liver are, and how they function.
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لذا فإن الكبد هو أكبر عضو في جسمك. إنه حوالي كيلو ونصف. نوع من ثلاثة أرطال. إنها بحجم كرة الرجبي ، وحوالي 1/50 من كتلة جسمك. ينمو ليناسب حجمك. تتكون من حوالي 100 مليار خلية. وهو أكبر عضو صلب لديك. لذا إذا أخرجت رئتي ديف هنا ، يمكنك رؤية الكبد.
، ينفصل إلى فصين مختلفين ، الفص الأيمن والأيسر ، مفصولين عن طريق هذا الرباط هنا ، الرباط المنجلي. وهي مرتبطة ارتباطًا وثيقًا بأعضاء البطن الأخرى هذه. وفي الواقع ، إذا قلبتها ، يمكنك أن ترى أن هناك اكتئابًا حيث تضغط الكلى والأمعاء على الكبد. يتم تثبيته في مكانه عن طريق الضغط داخل البطن والحجاب الحاجز والصفاق. وهي في الواقع محمية بواسطة كبسولة كولاجينية ، والتي تحافظ على السطح محميًا. إذا قلبت الكبد ، يمكنك أن ترى النقطة التي يدخل فيها الدم ويغادر الكبد. والكبد غير معتاد من حيث أن لديه إمداد دم مزدوج...
إذاً لديك دم مؤكسج يدخل عبر الشريان الكبدي ، ولكن لديك أيضًا دم غني بالمغذيات ، يأتي مباشرة من الأمعاء ، ويدخل أيضًا عن طريق الوريد البابي. وبعد ذلك يكون لديك المخرج حيث تخرج العصارة الموجودة في الكبد وتدخل إلى المرارة. هذه هي المرارة هنا. يمكنك أن ترى أنه يجلس تحت الكبد في الخلف. يبلغ طوله حوالي 10 سم. إنها مثل حقيبة صغيرة. وتقوم بتخزين حوالي 50 مليلترًا من الصفراء ، والتي تصنعها طوال اليوم. وهو نوع من عصره وإفرازه في أمعائك بالأسفل هنا ، حيث تحتاجه عندما تأكل. لذلك يتم تحفيزها من خلال وجود الطعام في الأمعاء.
تنقبض العضلة العاصرة الصغيرة وتقوم بالفعل بإيصال هذه الصفراء إلى الأمعاء حيث يمكن أن تساعدك على هضم الدهون. لذلك إذا تحدثنا عن إمداد الدم مرة أخرى ، أكثر قليلاً ، حوالي 75٪ من دمك يأتي فعليًا عبر هذا الوريد البابي. إذن هذا هو الإمداد الذي يأتي من أمعائك. في حين أن حوالي 25٪ من الدم مؤكسج وهذا ما يدخل من خلال الشريان الكبدي. ثم يدخل الدم من خلال هذين المسارين ويختلط داخل جسم الكبد قبل أن يستنزف ويخرج من الكبد عبر الوريد الأجوف السفلي ، ويعود إلى الدورة الدموية الجهازية.
بناءً على هذا الإمداد بالدم وهذا التصريف الصفراوي ، يمكنك في الواقع تقسيم الكبد إلى أقسام تشريحية. لذا فبدلاً من هذا النصف الأيسر والأيمن فقط ، يمكنك في الواقع تقسيمها إلى أجزاء منفصلة ، كل منها لديها إمدادات الصفراء وإمدادات الدم الخاصة بها. وهذا مفيد حقًا للجراحة وعلاج أشياء مثل الأورام ، لأنه يمكنك بالفعل استئصال جزء من الكبد ، ربما يحتوي على ورم فيه ، بإمداد دم مستقل خاص به ، والباقي من الكبد ليس كذلك تسوية. وسنتحدث عن كيفية نمو الكبد أو تجدده في وقت لاحق من الدورة. لقد قمت الآن بتغطية تشريح الكبد.
لكن ما يتعين علينا القيام به بعد ذلك هو الحديث عن التشريح المجهري للكبد. لذا فإن الطريقة التي ننظر بها إلى هذا هي أخذ عينة من الكبد يمكننا وضعها تحت المجهر. وعادة ما يتم ذلك عن طريق خزعة الكبد. إذن ما سيفعله طبيبك هو استخدام إبرة لأخذ عينة بالفعل. كان يمر بين الضلوع هنا ، ويأخذ عينة من هذا النصف الأيمن الأكبر من الكبد ، والذي يمكن حفظه بعد ذلك ، ووضعه تحت المجهر. ومن ثم يمكننا في الواقع إلقاء نظرة على الخلايا ومحاولة معرفة ما يحدث.
الكبد تحت الميكروسكوب
وتغير الخلايا الكبدية
some of the hepatocytes have got holes in them, like this one here or this one here or down here. These holes actually in life were occupied by lipid droplets which dissolved during our processing procedure. And this is known as fatty change. Fatty change is extremely common in Western communities. The two main causes being excess alcohol consumption, but increasingly the commonest cause now are complications related to the metabolic syndrome characterised by obesity, type 2 diabetes, hyperlipidemia, and various other features. And this woman was known to be overweight.
And this is almost certainly the cause of the fatty change we’re seeing here.
Yes, certainly. So this sample came from a man who was known to have longstanding liver disease. He suffered from a condition called primary sclerosing cholangitis, which is a reasonably common cause of chronic liver disease in the United Kingdom. It’s frequently associated with another condition known as ulcerative colitis, which is an inflammatory condition affecting the colon. In the case of this man, attempts to manage the condition using medical treatment eventually proved to be unsuccessful. And he developed end-stage liver disease for which the only currently effective treatment is liver transplantation.
So this differs from the previous case in two ways. The first thing I should point out is that the method we have used to stain this particular section is different to the conventional hematoxylin and eosin stain. In this case, the section has been stained with a method known as hematoxylin Van Gieson. And using this method, we are able to highlight collagen fibres which stain red. Now in the normal liver, these red collagen fibres are confined to portal tracts, which as I explained in the previous case, contain branches of the bile duct, the hepatic artery, and portal vein. And they’re also present in the walls of the hepatic veins, which drain blood.
But in this particular liver, you can see that there’s a lot more red collagen than there should be. And in fact, what’s happened is that this red collagen has replaced normal hepatocytes. And what we’re left with are small nodules– these green areas of surviving hepatocytes– many of which are completely surrounded by bands of fibrous tissue.
بعض خلايا الكبد بها ثقوب ، مثل هذه الموجودة هنا أو هذه هنا أو هنا. هذه الثقوب في الحياة كانت مشغولة بقطرات دهنية تذوب أثناء إجراء المعالجة. وهذا ما يعرف بالتغيير الدهني. التغيير الدهني شائع للغاية في المجتمعات الغربية. السببان الرئيسيان هما الإفراط في استهلاك الكحول ، ولكن السبب الأكثر شيوعًا الآن هو المضاعفات المتعلقة بمتلازمة التمثيل الغذائي التي تتميز بالسمنة ، ومرض السكري من النوع 2 ، وفرط شحميات الدم ، ومختلف الميزات الأخرى. وكان من المعروف أن هذه المرأة تعاني من زيادة الوزن.
ومن المؤكد أن هذا هو سبب التغيير الدهني الذي نراه هنا.
نعم بالتأكيد. لذلك جاءت هذه العينة من رجل كان معروفًا بإصابته بمرض الكبد منذ فترة طويلة. لقد عانى من حالة تسمى التهاب الأقنية الصفراوية المصلب الأولي ، وهو سبب شائع إلى حد ما لمرض الكبد المزمن في المملكة المتحدة. غالبًا ما يرتبط بحالة أخرى تُعرف باسم التهاب القولون التقرحي ، وهي حالة التهابية تصيب القولون. في حالة هذا الرجل ، ثبت في النهاية فشل محاولات إدارة الحالة باستخدام العلاج الطبي. وقد طور مرض الكبد في مراحله الأخيرة ، والعلاج الوحيد الفعال له حاليًا هو زراعة الكبد.
لذلك هذا يختلف عن الحالة السابقة من ناحيتين. أول شيء يجب أن أشير إليه هو أن الطريقة التي استخدمناها لتلطيخ هذا القسم بالذات تختلف عن صبغة الهيماتوكسيلين والأيوزين التقليدية. في هذه الحالة ، تم تلوين القسم بطريقة تعرف باسم الهيماتوكسيلين فان جيسون. وباستخدام هذه الطريقة ، يمكننا إبراز ألياف الكولاجين التي تلطخ اللون الأحمر. الآن في الكبد الطبيعي ، تقتصر ألياف الكولاجين الحمراء هذه على المسالك البابية ، والتي كما أوضحت في الحالة السابقة ، تحتوي على فروع القناة الصفراوية والشريان الكبدي والوريد البابي. وهم موجودون أيضًا في جدران الأوردة الكبدية ، التي تستنزف الدم.
What does the
ولكن في هذا الكبد بالذات ، يمكنك أن ترى أن هناك الكثير من الكولاجين الأحمر أكثر مما ينبغي أن يكون. وفي الواقع ، ما حدث هو أن هذا الكولاجين الأحمر قد حل محل خلايا الكبد الطبيعية. وما تبقى لنا هو عقيدات صغيرة - هذه المناطق الخضراء من خلايا الكبد الباقية - والتي يحيط الكثير منها تمامًا بشرائط من الأنسجة الليفية.
Hepatic cell
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.
What does the liver do ?
So this should give you a big clue to one of the major functions that it has, which is actually to help you with digestion and utilisation of your food materials.
So sugar is a good example of this. So if you have sugar in your diet from something like this apple, it will travel to your liver from your intestine and to the back of the liver. And then what the liver can actually do is store that sugar until you need it. So what it does is it converts the glucose into a polysaccharide called glycogen, which it can store overnight until there’s a situation where you may need that sugar, so where you’re sleeping and not eating. And it can gradually release that sugar, convert it back to glucose, and release it back into your bloodstream as you need it to help maintain your sugar levels in your blood.
So that sort of hints at a kind of digestive and storage function of the liver. And it’s also really good actually at storing other components that you might find here. So vitamins and minerals can also be stored in the liver. The other situation, you may not have such a good diet as this. You may have eaten too much fat. And the liver can actually use that fat as an energy source. So it can break it down and use the energy. But if you have too much fat, then you actually get a situation where the fat can be stored inside the hepatocytes.
And it forms a little sort of bubble of triglyceride, which again can be broken down and can be used for energy. But if that becomes too much of a problem, so if you have too much fat in your diet, and there’s an excess of lipid flying around, then you get something called fatty liver disease. And we’re going to hear about this a bit more, when we talked to a liver pathologist, Stefan Hubscher, but also when we talk to one of the physicians who treats liver disease later on. So minerals, vitamins, glucose can all be stored in the liver.
So if we then move on to think about another function of your liver– we talked about this also briefly in our first video. And this is to do with bile, which if you remember is stored in the gallbladder at the back of the liver. So one of the functions of bile is to help you cope with those fats, actually. So when you eat, your gallbladder will contract. And it squirts bile down into your small intestine to help you make that fat soluble, or at least emulsify it so that you can actually use it for food. The other thing people often talk about when they’re considering the liver is it’s actually something of a factory.
So it makes important proteins for the body. So a good example of this is the proteins that actually help your blood to clot. So they’re produced by those hepatocytes within the liver. And then they’re secreted into the circulation, out into the periphery. So if you get an injury or a wound, those factors are available to actually help your blood clot. And this is one of the reasons why patients with liver disease may have a bit of a challenge if they have to have surgery, or if they have to have a liver biopsy. Because obviously if their clotting is compromised, then that makes these procedures risky.
So liver physicians will always make sure that a patient is clotting properly before they would attempt surgery, for example.
So the next function we’ll talk about relates to these bottles of alcohol that we have here, but also these drugs that we have in front of us. So one of the major things your liver does to keep you healthy is it actually detoxifies chemicals that enter your system. So this could be alcohol you drink, a prescription medication that your clinician prescribed for you, or it could even be cosmetics that you put on your skin. Everything makes its way into the bloodstream and ends up in the liver. And then what the liver can do– again, in those hepatocytes, there are enzymes which can actually break down these chemicals.
They can either use something which is useful– so for example, calories from something like alcohol can be utilised. Anything else is broken down and converted into a form in which it can be excreted through your kidneys. So through that means, your liver protects your body from anything harmful that comes into it through this ability to actually detoxify chemicals. So to summarise what we’ve covered today, we’ve basically tried to illustrate the major functions of the liver for you. So we’ve talked about its role in digestion. We’ve talked about the fact that it can help you store important things, so vitamins and minerals, for example. We’ve shown you how actually one of its major roles is actually to detoxify chemicals.
And we’ve considered how all of these actually keep you healthy. But the next thing that we’re going to consider in our next exercise is actually one of the things which characteristically happens when your liver is not working properly. This is something you may have heard of called jaundice, which is where you actually get a very characteristic yellowing of the skin and the whites of the eyes. So our next exercise will actually explain to you what causes that and why it
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