Liver produces important proteins, such as albumin, which ensures you don’t look swollen, and allows for the transport of important drugs. It helps to detoxify things that may be dangerous to your health. It also helps to give you energy by generating glucose, and so much more! 

What Is Bile and Bilirubin?

Other than all of the things that I just mentioned the liver is important for, it’s also important for the production of something known as bile. This is a greenish liquid produced in the liver and stored in the gallbladder, which facilitates the digestion of fat. 

Bile, among other things, contains something known as bilirubin. Bilirubin is an orange-yellow pigment formed from the breakdown of red blood cells. Bilirubin is converted into other substances that eventually give urine its yellow color and feces its yellow-brown color. Who knew physiology could be so colorful and yet so disgusting? 

When red blood cells break down due to age or destruction, then something known as unconjugated or indirect or water-insoluble bilirubin is released into the bloodstream. Once this unconjugated bilirubin enters the liver, the liver converts it into conjugated or direct or water-soluble bilirubin by tacking on a compound known as glucuronic acid; this is what makes bilirubin water soluble. 

This newly water-soluble bilirubin is then secreted into the watery bile and, from there, into the intestines. 

If all of this is making your head spin, don’t worry; we can simplify it even more. Your liver is like a giant factory. Through one end, raw ingredients come in by the truckload. In our case, that’s crates and crates of raw, hard, and unprocessed indirect bilirubin. Once inside the factory, the workers take a piece of unconjugated bilirubin and stick another ingredient right onto it, thereby making an entirely new concoction, called conjugated bilirubin. This conjugated bilirubin isn’t hard like unconjugated bilirubin; it’s slushy and can dissolve easily in water instead. 

If the levels of either the conjugated or unconjugated bilirubin increase in the body, they can cause icterus, which is the more technical term for jaundice. If you are not sure of what jaundice is, then let me explain. Jaundice is the yellowing of the whites of the eyes, mucous membranes, and a person’s skin as a result of abnormally increased levels of bilirubin in the blood, aka hyperbilirubinemia. 

What Causes Unconjugated Hyperbilirubinemia?

Based on what I’ve said thus far, you should be aware that the ways by which levels of unconjugated bilirubin can increase are: 

1. if something causes indirect bilirubin levels to rise before they reach the liver 
2. if unconjugated bilirubin isn’t being delivered properly to the liver (both of which are also known as pre-hepatic causes) 
3. if there’s something wrong with the liver that disables the conversion mechanism to conjugated bilirubin (also known as hepatic causes) 

Types of Jaundice

Pre-Hepatic

• In pre-hepatic jaundice, there is excessive red cell breakdown which overwhelms the liver’s ability to conjugate bilirubin. This causes an unconjugated hyperbilirubinaemia.
• Any bilirubin that manages to become conjugated will be excreted normally, yet it is the unconjugated bilirubin that remains in the blood stream to cause the jaundice.

Hepatocellular

• In hepatocellular (or intrahepatic) jaundice, there is dysfunction of the hepatic cells. The liver loses the ability to conjugate bilirubin, but in cases where it also may become cirrhotic, it compresses the intra-hepatic portions of the biliary tree to cause a degree of obstruction.
• This leads to both unconjugated and conjugated bilirubin in the blood, termed a ‘mixed picture’.

Post-Hepatic: Post-hepatic jaundice refers to obstruction of biliary drainage. The bilirubin that is not excreted will have been conjugated by the liver, hence the result is a conjugated hyperbilirubinaemia.

Laboratory Tests

Any patient presenting with jaundice should have the following bloods taken:

• Liver function tests (LFTs), as summarised in Table 2
• Coagulation studies (PT can be used as a marker of liver synthesis function)
• FBC (anaemia, raised MCV, and thrombocytopenia all seen in liver disease) and U&Es
• Specialist blood tests, as summarised below as part of a liver screen

Blood Marker	Significance
Bilirubin	Quantify degree of any suspected jaundice
Albumin	Marker of liver synthesising function
AST and ALT	Markers of hepatocellular injury*
Alkaline Phosphatase	Raised in biliary obstruction (as well as bone disease, during pregnancy, and certain malignancies)
Gamma-GT	More specific for biliary obstruction than ALP (however not routinely performed)

Table 2 – LFT serum markers. *as an estimate, if the AST:ALT ratio >2, this is likely alcoholic liver disease, whilst if AST:ALT is around 1, then likely viral hepatitis as the cause

Liver Screen

A liver screen can be performed for patients whereby there is no initial cause for liver dysfunction, tailored to whether acute or chronic liver failure

	Viral Serology	Non-Infective Markers
Acute Liver Injury	Hepatitis A, Hepatitis B, Hepatitis C, and Hepatitis ECMV and EBV	Paracetamol levelCaeruloplasminAntinuclear antibody and IgG subtypes
Chronic Liver Injury	Hepatitis BHepatitis C	CaeruloplasminFerritin and transferrin saturationTissue Transglutaminase antibodyAlpha-1 antitrypsinAutoantibodies*

Table 3 – Acute and Chronic Liver Screens *Autoantibodies include anti-mitochondrial antibody (AMA), anti-smooth-muscle antibody (Anti-SMA), and anti-nuclear antibody (ANA), used to identify a variety of autoimmune liver conditions, such as primary sclerosing cholangitis (PSC)

Imaging

The imaging used will depend on the presumed aetiology. An ultrasound abdomen is usually first line, identifying any obstructive pathology present or gross liver pathology (albeit often user dependent).

Magnetic Resonance Cholangiopancreatography (MRCP) is used to visual the biliary tree, typically performed if the jaundice is obstructive, but US abdomen was inconclusive or limited, or as further work-up for surgical intervention.

A liver biopsy can be performed when the diagnosis has not been made despite the above investigations.

Management

The definitive treatment of jaundice will be dependent on the underlying cause. Obstructive causes may require removal of a gallstone through Endoscopic Retrograde CholangioPancreatography (ERCP) or stenting of the common bile duct.

Symptomatic treatment is often needed for the itching caused by hyperbilirubinaemia. An obstructive cause may warrant cholestyramine (acting to increase biliary drainage), whilst other causes may respond to simple anti-histamines.

Identify and manage any complications where possible. Monitor for coagulopathy, treating promptly (either vitamin K or fresh frozen plasma (FFP) is needed) if any evidence of bleeding or rapid coagulopathy, and treat hypoglycaemia orally if possible (otherwise 5% dextrose is needed).

Where patients become confused from decompensating chronic liver disease (‘hepatic encephalopathy’), laxatives (lactulose or senna) +/- neomycin or rifaximin may be used, in attempt to reduce the number of ammonia-producing bacteria in the bowel.By User:Pschemp [CC-BY-SA-3.0], via Wikimedia Commons