Cholestasis/jaundice
First, we’ll talk about jaundice, then cholestasis (one of the causes of jaundice).
Normal plasma bilirubin concentration is usually less than 1.5 mg/dL, increased above this we have bilirubinemia, if the
bilirubinemia becomes large enough (usually about 2.5-3 mg/dL) we expect jaundice.
The image to the right provides a reminder for the metabolism of bilirubin, it is the product of heme degradation, where it forms and unconjugated state, before being conjugated in the liver where it is then secreted via the biliary system as conjugated bilirubin and fecal and kidney excretion. Interruptions to this can be put into three categories:
Image: “Bilirubin metabolism” by Michlwt, CC BY-SA 4.0, via Wikimedia Commons.
- Increased bilirubin production
- Error in hepatocyte metabolism
- Error of excretion
Another way of labelling these is unconjugated and conjugated jaundice.
The main symptoms of jaundice are a yellowish discolouration of the sclera, darker urine, and yellowish skin.
Below we shall consider some of the more unusual causes of jaundice, and how we tackle such patients. The main differential diagnosis of jaundice is shown below.
To distinguish between prehepatic, hepatic and post hepatic, we can use the following labs:
- Prehepatic:
- Urine does not have bilirubin, serum increased unconjugated bilirubin
- LFTs normal
- Hepatic and post Hepatic
- Urine has conjugated bilirubin, plasma albumin level is low but plasma globulins are raised
- Only difference is that unconjugated bilirubin is normal in post hepatic form, increased in hepatic form.
- LFTs abnormal
Common causes of jaundice:
- Hepatic
- Damaged hepatocytes
- Hepatitis, cirrhosis, hepatic carcinoma
- Metabolic hepatocyte disorders
- Post-hepatic
- Intrahepatic
- Swelling, fibrosis or obstruction of liver canaliculi
- Extrahepatic
- Cholestasis
- Occlusion
- Calculus cholecystitis
- Compression
- Edema of pancreatitis
- Carcinoma of head of pancreas
- Acalculous cholecystitis
- Prehepatic
- Excess hemolysis
Below we have considered some of the types of jaundice that we may not be familiar with.
Genetic disorders of bilirubin conjugation
- Five syndromes that cause hyperbilirubinemia due to hepatocyte metabolic error
- Crigler-Najjar and Gilbert syndromes
- Cause unconjugated hyperbilirubinemia
- Reduction in enzymatic activity (UGT1A1) means high levels of unconjugated bilirubin
- Crigler-Najjar syndrome Type 1, 2 or Gilbert syndrome (Gilbert most common, 12% of population)
- Gilbert is most common of these genetic disorders, typically no treatment is needed, although if jaundice is significant, phenobarbital can be given.
- Unconjugated hyperbilirubinemia in the newborn period
- Mildly increased bilirubin between days 2-5 due to hepatic immaturity and low UGT1A1 levels (enzyme responsible for bilirubin conjugation)
- Conjugated or mixed hyperbilirubinemia
- Dubin-Johnson syndrome and Rotor syndrome