Jaundice- Initial Approach to identify cause Flashcards
What is jaundice?
Jaundice is a yellow pigmentation to the skin, sclera and mucoussa that occurs when bilirubin levels are increased
Beyond what level of serum bilirubin do the clinical manifestations of jaundice appear?
> 60umol/L
How can you divide the causes of jaundice?
Pre Hepatic
Hepatic
Post Hepatic
Or whether there is a predominantly raised conjugated or unconjugated bilirubin
Why is a split bilirubin useful for determining the cause of jaundice?
The hepatocytes are responsible for the conjugation of bilirubin. Depending upon the location of the issue unconjugated or conjugated bilirubin will be raised, it therefore helps to localise the problem
Where does bilirubin come from?
The breakdown of red cells releases haemoglobin- a breakdown product of this is bilirubin
What is heme broken down into within the macrophages?
Protoporphyrin and Iron
Protoporphyrin is then converted to unconjugated bilirubin
What is protoporphyrin converted to? Where does it come from?
Unconjugated bilirubin
It comes from the breakdown of haeme (from haemoglobin)
Where does bilirubin conjugation take place?
The liver
What enzyme is responsible for the conjugation of bilirubin?
UGT
Which form of bilirubin is water soluble, and so will appear in the urine?
Conjugated bilirubin is water soluble
What happens to conjugated bilirubin in the small intestine?
Converted to urobilinogen
What is the fate of urobilinogen within the GI tract?
Some is converted to stercobilin- causes stools to appear brown
Some is reabsorbed and is oxidised to urobilin. Some of this goes to the kidneys and some to the liver. That which travels to the kidneys appears in the urine and causes the urine to appear yellow.
What type of jaundice is associated with a raised unconjugated bilirubin?
Pre-Hepatic
What are some causes of pre-hepatic jaundice?
Haemolytic Anaemias Ineffective Haematopoeisis Gilberts (defective UGT) Crigler Najar (deficient in UGT) Increased erythropoiesis
Why is unconjugated bilirubin raised most in pre-hepatic causes?
Level of unconjugated bilirubin exceeds the capacity of the hepatocytes to conjugate it, causing increased serum levels
Why does urine appear darker for pre-hepatic causes of jaundice?
Conjugated bilirubin (converted to urobilinogen) levels increase when there is an increased haem load, this causes increased levels of urobilinogen in the GI tract which is reabsorbed, oxidised to urobilin and some is excreted in the urine- causing it to appear darker
If suspecting a pre-hepatic cause what investigations should be requested to check for increased red cell breakdown?
FBC
Hb
Haptoglobin- decreases with increased red cell turnover
LDH- increases with cell breakdown
Reticulocyte count- increases with increased red cell breakdown
Blood smear
Direct Coombs Test (DCT) - to check for presence of antibodies against the red cells
What is the underlying process in physiological jaundice of the newborn?
Low UGT levels and breakdown of fetal red Hb causes jaundice, treatment with phototherapy to prevent levels exceeding dangerous amounts
Unconjugated bilirubin is fat soluble and can collect in the basal ganglia to cause Kernicterus
What is the complication that can occur with prolonged periods of raised unconjugated bilirubin?
Kernicterus- the fat soluble unconjugated bilirubin deposits in the basal ganglia
What is the main treatment for physiological jaundice of the newborn?
Phototherapy
What genetic disorders can cause increased levels of unconjugated bilirubin?
Gilberts- defective UGT
Crigler Najjar- deficient UGT
What triggers jaundice to develop in patients with Gilbert’s?
Stress on the body- infection, stress, starvation due to increased haemolysis exceeding the conguating capacity of the defective UGT
Why are you unlikely so see a case of Crigler Najjar Syndrome?
They don’t live very long as they develop fatal kernicterus
What blood tests should be requested to localise the cause of jaundice?
Total Bilirubin Conjugated and Unconjugated Bilirubin ALT AST GGT ALP Albumin INR, PT, PTT
What enzymes are markers of liver injury?
ALT
AST
What blood tests are markers of hepatocellular function?
Albumin
INR
PT
PTT
What are the two main causes of prehepatic jaundice?
Haemolytic Anaemia
Dyserythropoiesis
What are some causes of dyserythropoiesis? Why does it cause a raised unconjugated bilirubin?
Hereditary Spherocytosis
Hereditary Elliptocytosis
Sickle Cell
G6PD Deficiency- inability to handle oxidative stress
The damaged or dysfunctional cells are more degraded by the reticuloendothelial system to produce haem which is broken down to unconjugated bilirubin
How can the causes of haemolytic anaemia be divided?
Autoimmune
Alloimmune- transfusion reactions, haemolytic disease of the newborn
Drug induced (which triggers an immune reaction)
What blood tests would you request if suspecting a haemolytic cause? Describe how they would change if there was a haemolytic process
FBC- Low Hb LDH- Increased Haptoglobin- Decreased Reticulocyte Count- Increased Blood Smear- For structural problems DCT- For autoimmune causes
What genetic conditions can cause a raised conjugated bilirubin with no evidence of hepatocellular dysfunction?
Dubin Johnson Syndrome and Rotor Syndrome
Protein (MRP2 for DBS) that normally transports conjugated bilirubin into the bile is defective in both. The conjugated bilirubin then ends up on the blood stream- excreted in urine causing very dark urine
What test is used to investigate for Dubin Johnsons Syndrome?
Urinary Coproporphyrins- normal in quantity but different quality due to altered levels of different forms
CP 1 normally excreted in the bile but is found in the urine in DBS
What is test is use to investigate for Rotor Syndrome?
Urinary Coproporphyrins- normal in quality and quantity
What blood tests results suggest a hepatic cause for jaundice?
Raised total bilirubin
Raised conjugated bilirubin (think of damage to hepatocytes causing it to leak out into the blood)
Raised ALT/AST
May be: (If liver dysfunction)
Decreased Albumin
Deranged clotting
What are some hepatic causes of jaundice?
Viral hepatitis- Hep B, C Autoimmune Hepatitis Alcoholic Hepatitis NAFLD Cirrhosis Haemochromatosis Wilson Disease Primary Biliary Cholangitis Hepatic Malignancy
What blood results suggest a post-hepatic cause of jaundice?
Raised conjugated bilirubin
Highly raised ALP/GGT
Mildly raised or normal AST/ALT
What are some causes of post-hepatic jaundice?
Painful- Gallstones
Painless- Pancreatic cancer, PBC, PSC, Cholangiocarcinoma (Tumour of Bile Duct)
What tumour markers may be elevated for cholangiocarcinomas?
C19-9
CEA
What is normally the first line investigation for a suspected obstructive jaundice?
Abdominal USS
What investigation allows for detailed assessment of the structure of the biliary tree?
MRI/ MRCP- This will show any blockages or strictures within the biliary tree
How is the prognosis for cholangiocarcinomas?
Poor as they are often metastatic at diagnosis
Why does PSC cause a cholestatic picture?
Autoimmune disease that targets the intra and extrahepatic bile ducts causing strictures and fibrosis
What investigation can be done to investigate for PSC?
MRCP to show if there are structures in the biliary tree
What are some symptoms of pancreatic cancer?
Epigastric abdominal pain
Weight loss
Jaundice (Painless)
What blood tests can be raised in pancreatic cancer?
Serum lipase
Ca 19.9
What is the name of the surgical procedure carried out to manage pancreatic cancer?
Whipple’s Procedure
What simple imaging test can be used to investigate for obstruction of the biliary tree?
Abdominal USS
