JAUNDICE Flashcards
What is the normal range of total bilirubin in the blood?
3-17 micromol/L
Where does bilirubin come from?
Haemoglobin which is unconjugated to bilirubin by splenic macrophages
How is bilirubin carried in the blood?
Bound to albumin
Where is bilirubin conjugated and by what enzyme?
In the liver by glucuronyltransferase
How is conjugated bilirubin secreted from the liver?
In bile.
What happens to conjugated bilirubin that is secreted in the bile?
It is turned into urobilinogen.
What happens to urobilinogen?
Either reabsorbed or excrete with faeces as stercobilin. If it is reabsorbed it either returned to liver and re-secreted into bile or excreted with urine.
What causes jaundice?
Increased levels of bilirubin over about 50 micromol/L due to break down of red blood cells. Both unconjugated and conjugated.
What are the features of jaundice?
Yellow skin
Yellow sclera
Itching
What are the causes of pre-hepatic jaundice?
Haemolysis
Ineffective erythropoeisis
Congenital unconjugated hyperbilirubinaemia (sometimes considered a hepatic cause but causes a pre-hepatic picture)
What is the most common form of congenital unconjugated hyperbilirubinaemia?
Gilbert’s syndrome
What is Gilbert’s syndrome?
A defect in UDP glucuronyltransferase enzyme which conjugates bilirubin. This leads to less conjugation and therefore increased levels of unconjugated bilirubin. Unconjugated bilirubin cannot be excreted as it is water soluble so there is a build up leading to jaundice.
What is the inheritance of Gilbert’s syndrome?
Autosomal recessive (although some dominance has been reported)
Are people with Gilbert’s syndrome affected by jaundice all of the time?
No. Only during intercurrent illness eg flu like symptoms or after a fast.
What investigations would you in someone to confirm a diagnosis of Gilbert’s syndrome?
Look for a bilirubin rise following a prolonged fasting.
DNA testing
What is the treatment for Gilbert’s syndrome?
No treatment is necessary, only reassurance. Carbamazepine and Phenobarbital can reduce unconjugated bilirubin levels. Diet changes are useful as well.
What are the hepatic causes of jaundice?
Viral hepatitis Alcoholic hepatitis Autoimmune hepatitis Drug induced hepatitis Decompensated cirrhosis Wilson's disease Dubin-Johnson syndrome
What are the viruses that can cause jaundice?
Hepatitis A, B, C or E
EBV
Cytomegalovirus
Herpes simplex/zoster
What is Wilson’s disease?
Autosomal recessive genetic disorder in which copper accumulates in tissues; this manifests as neurological or psychiatric symptoms and liver disease.
What is the main medication used to treat Wilson’s disease?
Penicillamine
What is Dubin-Johnson syndrome?
A defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile, and is similar to Rotor syndrome. Leads to conjugated bilirubinaemia but no changes in LFTs.
What are the drugs that can induce jaundice of hepatic cause?
Paracetamol OD Isoniazid Rifampicin Pyrazinamide Valproate Statins Halothane MOAIs
What are the post-hepatic causes of jaundice?
Intra-hepatic:
Primary biliary cirrhosis
Primary sclerosing cholangitis
Cholangiocarcinoma
Extra-hepatic:
Gallstones
Carcinoma of head of pancreas
Enlarged lymph nodes at porta hepatis
Drug causing cholestasis:
Oral contraceptive pill
Flucloxacillin or co-amoxiclav
Anabolic steroids
What is primary biliary cirrhosis?
Slowly progressive autoimmune disease of the biliary system with a chronic course which may extend over many decades. It involves destruction of the small interlobular bile ducts (canals of Hering) via the formation of portal granulomas. This causes intrahepatic cholestasis which damages cells, leading to scarring, fibrosis and eventually cirrhosis.
What do we look for in the blood in order to make a diagnosis of primary biliary cirrhosis?
Anti-mitochondrial antibodies
Other than anti-mitochondrial antibodies, what else might be abnormal in blood tests of someone with primary biliary cirrhosis?
High cholesterol
In someone suffering from primary biliary cirrhosis, what will liver function tests reveal?
Increased ALP Increased bilirubin (but later in the disease)
What is the classic history of a patient with primary biliary cirrhosis?
Young female with jaundice and itching
What is primary sclerosing cholangitis?
A chronic cholestatic liver disease with obliterative inflammatory fibrosis of the bile ducts. The term ‘primary’ is used to distinguish this condition from bile duct strictures that are secondary to bile duct injury, cholelithiasis or ischaemia.
Does primary sclerosing cholangitis affect the intra or the extra hepatic ducts?
Both
What disease is primary sclerosing cholangitis often associated with?
Ulcerative cholitis
What would a cholangiogram show in someone with primary sclerosing cholangitis?
Beads on a string appearance of ducts
In someone suffering from primary sclerosing cholangitis, what will liver function tests reveal?
Increased ALP
Increased bilirubin
What is the LFTs picture of pre-hepatic jaundice?
Increased unconjugated bilirubin
Increased lactate dehydrogenase
Increased AST
What is the urine picture of pre-hepatic jaundice?
No bilirubin (acholuric)
Increased urobilinogen
Increased Hb if caused by haemolysis
What investigations would you do in a jaundiced patient with LFTs and urinalysis showing a pre-hepatic picture?
FBC
Coombs tests
Hb electrophoresis
What is the LFTs picture of hepatic jaundice?
Increased conjugated bilirubin Increased AST Increased ALT (more ALT than AST in alcohol related) Increased GGT Increased ALP Decreased albumin Increased prothrombin time
What is the urine picture of hepatic jaundice?
Increased bilirubin
Increased urobilinogen
What investigations would you do in a jaundiced patient with LFTs and urinalysis showing a hepatic picture?
FBC - anaemia Autoantibody screen: anti-smooth muscle, anti-ANA α1-antitrypsin Ferritin Caeruloplasmin Liver biopsy
What is the LFTs picture of post-hepatic jaundice?
Big increase in conjugated bilirubin Increased AST Increased ALT Big increase in ALP Increased GGT
What is the urine picture of hepatic jaundice?
Big increase in bilirubin
No urobilinogen
What investigations would you do in a jaundiced patient with LFTs and urinalysis showing a post-hepatic picture?
Abdomen ultrasound - looking for ducts bigger than 6mm
ERCP, MRCP
Autoantibody screen: anti-mitochondrial antibodies, anti-ANCA, anti-ANA
