04 | Liver Disease 101: Understanding the structure and functions

Today we’re going to be diving in to our first clinical series - featuring one of my favourite organs, the liver.

 

The liver is perhaps one of our more underrated organs. It is an absolute powerhouse, and is responsible for SO many vital functions in the body. Which is why we can see such a variety of complications when it starts to go wrong.

Today, I'll introduce you to what the liver does, and how it does it - so that when we start moving on to different liver diseases, you can really understand why we see the signs we do (and what we need to be thinking about when we nurse these patients).

By the end of this episode, you’ll feel much clearer on how the liver works, and what it does, and how this impacts the nursing care we give patients with liver disease.

Let’s look at how our liver works…

1: Blood Supply

The liver has a unique vascular system; it receives about a quarter of cardiac output in total, receiving both oxygenated and deoxygenated blood.

This is unlike other organs where oxygen-rich blood is supplied via an artery, and deoxygenated, waste-product rich blood leaves via a vein.

So only around 20-30% of the blood that the liver receives is oxygenated blood via the hepatic artery - the rest (70-80% of the blood the liver receives) is deoxygenated blood via the portal vein.

The portal vein is a vessel that runs from the GI tract to the liver. Venous blood does not run directly from the GI tract to the caudal vena cava - because we need the nutrients from digestion to be appropriately distributed around the body, and we need any waste products from the digestion to be appropriately eliminated.

These are some of the liver’s most important functions - so it needs this unique blood supply, to receive that deoxygenated, nutrient and waste-rich blood from the intestines.

2: Structure

The liver is made up of 6 lobes:

  • the left lateral,

  • left medial,

  • right lateral,

  • right medial,

  • quadrate,

  • and caudate lobes.

These lobes are split into hexagonal sections called  lobules - and those functions - filtration of waste products and distribution of nutrients - happen in these lobules.

The lobules are made up of hepatocytes (or liver cells) which are arranged in cords. Between these cords are small vascular spaces called sinusoids - these sinusoids are lined with a thin, fenestrated epithelial membrane allowing filtration of substances between the liver cells and blood.

Each hepatic lobule also contains a central vein (which runs through the middle of the hexagon) and 6 ‘portal triads’ - one at each point of the hexagon.

Each portal triad is made up of 3 structures: a branch of the hepatic artery, a branch of the hepatic vein, and a bile ductule (which is kind of like a baby bile duct)

The blood from the portal vein enters the sinusoids between the liver cells, and the fenestrations in the sinusoid epithelial cells allow this blood to be ‘sieved’ - filtering out certain substances.

Nutrients and waste products are taken up into the liver for processing - at the same time, substances synthesised by the liver (like plasma proteins, or clotting factors) are deposited into the blood, so that they can be distributed around the body via the systemic circulation.

Inside those hepatic sinusoids are special defensive cells called Kupffer cells. These cells are a type of macrophage, and act as a first line of defense against debris, bacterial toxins and infectious agents from the GI tract. 

So what does the liver actually do?!

So we know that the main job of the liver is to filter and detoxify blood. But the liver is also responsible for a whole host of other functions, including:

  • Metabolising bilirubin and creating bile

  • Storing glucose as glycogen

  • Storing iron, vitamins and other essential nutrients

  • Synthesising essential proteins and enzymes, such as clotting factors and albumin

  • Processing lipids to form cholesterol and triglycerides

  • Synthesising ketones

  • Processing ammonia and creating urea

  • Storing blood

  • Eliminating tumour cells

  • Processing and removal of expired or damaged blood cells

  • Breakdown of amino acids to provide energy or create enzymes (deamination)

  • Regulation of platelet production

  • Breakdown of hormones within the body

  • And so much more

We’re going to look at a few of these important processes in more detail in this episode: forming bile, synthesising clotting factors, processing ammonia, and synthesising albumin.

Bilirubin metabolism and bile formation

Bilirubin is an insoluble waste product derived from the breakdown of red blood cells - specifically the breakdown of haemoglobin. In order for it to be excreted from the body, it needs to be made water soluble - through a process called conjugation which takes place inside the liver.

Bile channels called ‘cannaliculi’ lie between hepatocytes inside our liver lobules - and the conjugated bilirubin is deposited in these, alongside other bile components (like bile salts and bile acids) and water. Together, this forms bile - which flows through the cannaliculi to a bile ductile.

These bile ductles join together to form a network of progressively larger intrahepatic bile ducts.

The bile then leaves the liver via the common hepatic duct - which is attached to the gall bladder - where created bile is stored - via the cystic duct. These 2 ducts join together to form the common bile duct - through which bile enters the small intestine, where it helps to break down digested fats.

Bile is released into the small intestine in response to eating; most bile is then excreted in faeces; a small amount of bile acids are re-absorbed and turned back into bile in the liver.

Synthesising clotting factors

The liver is responsible for synthesising and secreting many clotting factors - including fibrinogen, factor V, VII, IX, X, XI and II, which are formed inside the hepatocytes themselves. Many of these factors are created from vitamin-K.

Antithrombin - a protein involved in clot inhibition and breakdown - is also created inside hepatocytes.

Other clotting factors, like factor VIII and von Willebrand’s factor, are created inside the cells that line the hepatic sinusoids.

Patients with disease impacting liver function can have a reduced ability to synthesise these clotting factors - as can patients with disorders like anticoagulant rodenticide toxicity.

That being said, clinically significant bleeding tendences in these patients are rare, but we certainly want to be checking coagulation times in patients where we’re thinking about biopsying the liver. Firstly, in case there are any issues in creating these clotting factors, but also because the liver is a site of blood storage, so haemorrhage from hepatic biopsies/surgery is a significant risk.

Processing ammonia and forming BUN

Ammonia (NH3) is a waste product from dietary protein breakdown. The liver is responsible for taking this ammonia from the GI tract, via the portal vein, and turning it into urea (or BUN; blood urea nitrogen), a nitrogenous waste product, which can then be safely eliminated in the urine.

Ammonia is a neurotoxin - so if ammonia levels increase, we can begin to see neurological signs. This is known as hepatic encephalopathy.

The signs we can see in a hepatic encephalopathy patient include:

  • Dull mentation or decreased responsiveness

  • Ataxia

  • Head pressing

  • Ptyalism

  • Seizures

Now it’s worth noting that ammonia is not the ONLY compound involved in hepatic encephalopathy - there are other toxins involved too - but it is considered a primary agent.

Synthesising Albumin

Now, one of the functions of the liver I mentioned was the creation of certain proteins - and albumin is a pretty important one for us to know about.

Albumin is created inside the hepatocytes from amino acids. It is actually the most abundant plasma protein - and it’s responsible for maintaining something called colloidal oncotic pressure or oncotic pull.

When albumin levels significantly drop, we can see leakage of fluid out of the plasma into the surrounding interstitial fluid - causing problems like oedema.

Now, significant hypoalbuminaemia is rare in patients with liver disease - but it’s still worth noting that we can see changes to this parameter in patients with liver dysfunction.

What about when the liver goes wrong?

Now that we’ve looked at the structure of the liver, and a few of its many functions in more detail, it’s time to start thinking about the different liver diseases that we see.

We see a wide variety of liver diseases, ranging from acute or chronic hepatitis, to copper-associated hepatopthies, to hepatic lipidosis, portosystemic shunts, neoplasia, biliary diseases and much more.

We’ll be focusing on all of those in their own dedicated episodes, so don’t worry if you’re not as familiar with them - over the next few weeks you definitely will be!

But the take home message I want to leave you with on liver disease for today is this - not every liver disease affects the liver (or the patient!) in the same way.

Some will upset our patient’s hepatocytes, but leave other functions of our liver (like clotting factor synthesis or ammonia removal) untouched.

Others will leave our patient’s liver cells alone, but significantly impair their liver function - and understanding how the liver works, and what those functions are - is key to understanding how these different diseases impact our patients differently - and how we can adjust our nursing care and treatment accordingly.

So over the next few weeks, we’ll be diving in to how each of these different diseases affect our patient, what changes we see with the liver, and how this reflects in the patient’s blood results - as well as how we can best treat and nurse them.

Did you enjoy this episode? If so, I’d love to hear what you thought - screenshot it and tag me on instagram (@vetinternalmedicinenursing) so I can give you a shout out, and share it with a colleague who’d find it helpful!

Thanks for learning with me this week, and I’ll see you next time!

References and Resources

  1. Breton, A. 2019. The Liver. Vetfolio, Available from  https://www.vetfolio.com/learn/article/the-liver

  2. Center, S. 2023. Anatomy of the Hepatobiliary System in Small Animals. MSD Vet Manual, Available from: https://www.msdvetmanual.com/digestive-system/liver-structure-and-function/anatomy-of-the-hepatobiliary-system-in-small-animals

  3. Merrill, L. 2012. Small Animal Internal Medicine for Veterinary Technicians and Nurses. Iowa: Wiley-Blackwell

  4. Tholey, D. 2023. Liver Structure and Function. MSD Manual, Available from: https://www.msdmanuals.com/en-gb/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/liver-structure-and-function

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