HistoQuarterly: LIVER

Working in a histology lab means that I get to see a lot of what our body looks like under the microscope.  Quarterly I will share with you some of my photos from the microscopic world of our inner space and tell you a little bit about what we’re looking at.

This year is National Pathology Year, and the organisers have allocated each month with a theme.  January’s theme is New Year’s Resolutions and so this quarter I wanted to tie in with this somehow.  I’ve chosen to look at the liver because it’s the one organ that’s most likely to have been hit the hardest over the festive season, with many people drinking more alcohol than they normally would.  A new year’s resolution, therefore, might be to look after the liver and not drink as much alcohol.

The liver and alcohol

The liver is our largest internal organ and serves many functions.  The most commonly known function is its role in breaking down alcohol and ridding the body of the byproducts.  After gulping down your tipple, the alcohol is rapidly absorbed by the stomach and the small intestine.  It then enters the bloodstream and arrives at the liver via a vein, known as the hepatic portal vein.  The alcohol is then absorbed by the main bulk of cells in the liver – thousands of polygonal cells, called hepatocytes.

Rows of hepatocytes – roughly hexagonal in shape.

Hepatocytes do not store alcohol.  In fact, alcohol is extremely toxic to the liver and so it tries to get rid of it using a couple of enzymes, called alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are stored in the hepatocytes.  These enzymes break down alcohol into water, carbon dioxide and fat.

Now a first for HistoQuarterly – a simple comparison between the histology of a normal liver and the histopathology of a liver from someone who has experienced excessive alcohol consumption.

A healthy liver contains very little fat, if any at all. Fat, however, is the one byproduct of alcohol breakdown that the liver can store.  The liver can only cope with a certain amount of alcohol in any given hour, so if you were to consume alcohol faster than the liver can break it down, your liver will become overwhelmed by the volumes, eventually becoming inflamed and full of fat.

Fatty liver is due to the deposition of fat, seen here as white droplets. Normal hepatocytes become vacuolated and the difference between normal liver becomes very obvious.

Fat deposits are, therefore, a result of excessive alcohol consumption (see opposite).  When alcohol is consumed at such a rate, another alcohol-breakdown mechanism, called the microsomal ethanol-oxidising system (MEOS), kicks in and this pathway has far worse additional damaging consequences than the ADH pathway, including damage to hepatocyte cell membrane and inability to process other compounds such as drugs, steroids and carcinogens.

The beauty of the liver, however, is its ability to regenerate.  Even when part of the liver has been surgically removed, it has the incredible capability of growing back.  The liver is the only internal organ we have that can do this.  In the case of liver damage caused by alcohol, provided that the damage has not become too extensive (and thus irreversible), purely abstaining from alcohol will resolve the harm.  If alcohol consumption were to continue, the liver would begin to scar, become hard and have an increased likelihood of progressing to chronic liver disease, namely cirrhosis.  At this stage, the best chance of survival would be through a liver transplant.

Nutrient regulation

The liver also has a role in the digestive system.  Similarly to alcohol, the nutrients from our food are absorbed through the small intestines, enter the blood stream and head straight to the liver via the portal vein.  Here, the amounts of sugar (glucose) and amino acids in these nutrients are regulated.  If the blood sugar is high – under the stimulation of insulin – the hepatocytes will absorb the glucose and use it to generate the energy needed to produce glycogen.

           a) A PAS stain at low magnification showing the glucose stores as a pink (fuschia) mottled pattern.   b) a higher magnification of the dashed area on (a). In this image, you can just make out the hepatocytes.

The liver can store glycogen up to the point where it accounts for 5% of the total liver weight.  In my lab, we use a technique called Periodic Acid Schiff (PAS) to stain up the glycogen in liver sections (see opposite).  If blood sugar levels continue to rise beyond the 5% storage limit, the liver will use that excess to make triglycerides (ethanol and fatty acids), which become bound to proteins and re-released into the bloodstream.  Fatty tissue found around the body will then absorb these fats for storage.

When blood sugar is low – under the stimulation of glucagon – the fatty stores are then broken down and sugar is released once again into the bloodstream.

The amino acids are not as precisely controlled as sugar, it’s usually just our changing dietary protein that causes the levels in our blood to fluctuate.  Once the amino acids are absorbed, however, the liver uses them to make the proteins that play an important role in blood clotting, for example.

Blood regulation

MAIN: Polygonal hepatocytes organised in loose rows are separated by narrow spaces, called sinusoids, where blood flows through on its way to the larger hepatic venules.  The venules then lead the blood to the inferior vena cava, which is the large vein that takes deoxygenated blood to the heart.  INSET: a silver stain (called a reticulin stain) highlights only the outline of the hepatocytes (no nuclei).  They demonstrate a chicken-wire appearance.  BNH =  binucleate hepatocytes, which are perfectly normal.

Our liver is the largest blood reservoir in our bodies, through which all our blood will eventually pass.  This is useful for another function of the liver, which is to remove toxins from the blood.  In the case of circulating drugs, the liver combats them by breaking them down and limiting how long they remain effective for – this is why drugs have different dosage allowances because if a drug is absorbed quickly, it needs to be taken more regularly to keep the concentrations in the blood at the correct levels.  Similarly, a slowly absorbed drug will require longer intervals between administrations.  This rule is apparent for all types of drugs, including recreational drugs.  If you take more drugs than your liver can safely remove, you run a serious risk of overdosing, which results in damaged hepatocytes and even permanent liver failure – so be sure you stick to any guidelines, folks!!

Drugs are not the only products in our bodies that the liver works to remove.  Such things as hormones, antibodies and cell debris from the aftermath of an infection are also on the target list.  The antibodies and some of the hormones, such as adrenaline and insulin actually get recycled by the liver.

Fat digestion

A liver portal triad contains branches of the hepatic artery (brings oxygenated blood to the liver), portal vein (transports blood from the gut, pancreas and spleen) and bile duct (transports bile to the duodenum and/or gallbladder). The connective tissue simply supports the portal triad.  The interface is the row of hepatocytes immediately surrounding the triad (also known as the limiting plate).

Also as part of the digestive system, the liver can help control the amount of fat in our blood.  Periodically, the hepatocytes will produce a thick, greeny yellow fluid, called bile (about 1 litre a day).  This is drained into a small network of tiny tubes, known as bile canaliculi, which wrap around the hepatocytes, coming into contact with each cell at at least two points.  This meshwork of tubes converge to a single larger tube, called the periportal bile ductule (or canal of Hering or cholangiole).  These ductules then carry bile to the bile duct, which then transports it to the small intestine (more specifically, the duodenum), where it mixes with the partly digested food from the stomach and helps breakdown the fat.

Bile production occurs continuously, but its release into the duodenum only happens when stimulated by the hormone cholecystokinin, which relaxes the muscle at the opening into the duodenum (the hepatopancreatic sphincter).  Without this stimulation, bile backs up into another duct (the cystic duct) that leads to a little bile-storage sack, known as the gallbladder.   Cholecystokinin works to stimulate contractions in the gallbladder wall, which also helps to push the bile into the duodenum.

Storage

In addition to the storage of glycogen, the liver is also a good storage base for vitamins (A, D, E, K and B12) and iron, which are absorbed from the blood.  The vitamins are simply re-released whenever levels in the diet are low.  The iron, in fact, is toxic to our cells in its free form and so the liver facilitates the binding of it to a protein called ferritin, producing a complex that is much safer to store.  As with the vitamins, once circulating iron levels drop, the protein-iron complex is broken down to release the iron back into the blood.

Hormones

The liver also produces and secretes its very own hormones.  These include hormones involved in blood iron regulation, blood pressure regulation, protein production and bone development.

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With so many varied functions, you can appreciate just how vital our liver is and how it supports our other organs.  For more information about looking after your liver, please see the British Liver Trust.

If you want to find out if your relationship with alcohol is a healthy one or not, find out with NHS Choices here.

Thank you

Special thanks to @lozdorn for allowing me to use her iPhone to take photos of the PAS stain.

All images are Copyright © 2012 Della Thomas, unless otherwise stated.