Jaundice Flashcards
What are the three steps of bilirubin metabolism?
Production of unconjugated bilirubin
Conjugation of bilirubin
Excretion of bilirubin
How does unconjungated bilirubin travel to the liver?
Bound to albumin
Where are blood cells normally broken down?
In the spleen by splenic macrophages
What is bilirubin conjugated with in the liver?
Glucuronic acid
What is conjugated bilirubin converted to within the intestines and what happens to these products?
Urobilinogen and stercobilinogen
Some of the urobilinogen is reabsorbed by the intestines and excreted by the kidneys
Stercobilinogen gets converted to stercobilin, which gives faeces its brown colour
What are the three main types of jaundice?
Pre-hepatic
Hepatic
Post-hepatic (obstructive)
What characteristic clinical features are associated with obstructive jaundice?
Dark urine
Pale stools
What are the two mechanisms of unconjugated hyperbilirubinaemia?
Increased production of bilirubin (increased haemolysis)
Decreased capacity to conjugate bilirubin
Why might patients who are undergoing intravascular haemolysis have dark urine?
Free haemoglobin from the haemolysis is degraded into haemosiderin, which is water soluble and very dark
List some congenital causes of intravascular haemolysis.
G6PD deficiency
Pyruvate kinase deficiency
Sickle cell disease
Thalassemia
List some acquired causes of intravascular haemolysis.
Artificial heart valves Blood group mismatch DIC Malaria Medications
What might be seen on the blood film of a patient undergoing intravascular haemolysis?
Schistocytes
Which clinical sign is likely to be seen in patients undergoing extravascular haemolysis?
Splenomegaly
List a congenital and acquired cause of extravascular haemolysis.
Congenital – hereditary spherocytosis
Acquired – autoimmune haemolytic anaemia
What can cause reduced uptake of bilirubin by the liver?
TIPS (transjugular intrahepatic portosystemic shunt)
Name two congenital enzymatic problems that lead to unconjugated hyperbilirubinaemia.
Gilbert’s syndrome
Crigler-Najjar syndrome
Name a congenital cause of obstructive jaundice.
Dubin-Johnson syndrome
Using the surgical sieve, list causes of obstructive jaundice.
Infection – hepatitis, ascending cholangitis, liver abscess
Neoplasia – HCC, cholangiocarcinoma, pancreatic cancer
Vascular – Budd-Chiari syndrome
Inflammation/Autoimmune – PBC, PSC, autoimmune hepatitis, pancreatitis
Trauma – gallstones, strictures
Endocrine – intrahepatic cholestasis of pregnancy
Degenerative
Metabolic – haemochromatosis, Wilson’s disease
Drugs – alcohol, paracetamol, sodium valproate, co-amoxiclav
List some key features of the history of presenting complaint that you should ask a patient with jaundice.
Acute or chronic
RUQ pain, nausea and vomiting – suggests hepatobiliary
Fever and diarrhoea – suggest infection
Steatorrhoea, dark urine, pruritus – suggests obstructive
Weight loss, fever, night sweats – systemic features of malignancy
Bronzed skin and signs of diabetes mellitus – haemochromatosis
List three diseases, exclusive to pregnancy, that can cause jaundice.
Acute fatty liver of pregnancy
Intrahepatic cholestasis of pregnancy
HELLP syndrome (haemolysis, elevated liver enzymes, low platelets)
Why is it important to check for signs of diabetes mellitus?
Haemochromatosis can lead to diabetes mellitus
List some key features of the past medical history and explain why they might be significant.
Gallstones
Liver disease
Haemophilia – may have received contaminated blood products
Recent blood transfusion or surgery – possible transfusion reaction
Ulcerative colitis
Diabetes mellitus
Emphysema
Psychosis – may result from Wilson’s disease
List some drugs that increase the risk of jaundice by the following mechanisms: Intravascular haemolysis Autoimmune, extrvascular haemolysis Hepatitis Cholestasis
- Intravascular haemolysis Sulphonamides - Autoimmune, extravascular haemolysis Methyldopa - Hepatitis Paracetamol overdose - Cholestasis Co-amoxiclav
List some features of the social history that would be significant in a patient with jaundice.
Alcohol abuse IV drug use Tattoos Unprotected sex with multiple partners Recent foreign travel
List some features that you might see on examination of a patient with jaundice.
Signs of dehydration Fever Conjuctival icterus Cachexia Scratch marks Needle tracks Signs of chronic liver disease (spider naevi, palmar erythema, clubbing, bruising and gynaecomastia) Bronzed tan Kayser-Fleischer rings
Which causes of jaundice are supported by RUQ tenderness?
Hepatitis
Gallbladder disease – cholecystitis, ascending cholangitis
List some blood tests that may be useful in a patient with jaundice.
FBC and reticulocyte count
Serum bilirubin levels
Liver enzymes (AST, ALT, ALP, GGT)
Serum amylase or lipase
State which liver disease is likely if: Elevation of AST > ALT Elevation of ALT > AST Elevation of ALP + GGT Isolated elevation of GGT
- Elevation of AST > ALT Alcoholic liver disease - Elevation of ALT > AST Viral hepatitis - Elevation of ALP + GGT Biliary pathology - Isolated elevation of GGT Recent alcohol consumption
What does the finding of bilirubin in the urine indicate?
Post-hepatic obstruction
Which test must be performed in young women presenting with jaundice?
Pregnancy test – there are some causes of jaundice that are exclusive to pregnant women
List the components of the haemolysis screen.
Haptoglobins – these bind to free Hb and, hence, will be low in haemolytic states
Lactate dehydrogenase (LDH) – released by red cells when they lyse
Direct Antiglobulin test (Coombs test) – tests for autoantibodies against red cells (AIHA)
Blood film – look for schistocytes, sickle cells, spherocytes, malaria
Which diseases are tested for in viral serology?
Hepatitis A, B and C
EBV and CMV
HIV
Which antibodies should be tested for in an autoimmune screen of a jaundice patient?
Anti-smooth muscle antibodies (ASMA) – type 1 autoimmune hepatitis
Anti-mitochondrial antibodies (AMA) – primary biliary cirrhosis
Anti-nuclear antibodies (ANA)
Which test results would be consistent with:
Haemochromatosis
Alpha-1 anti-trypsin deficiency
Wilson’s disease
- Haemochromatosis High ferritin High transferrin saturation - Alpha-1 anti-trypsin deficiency Low alpha-1 anti-trypsin - Wilson’s disease High serum copper Low caeruloplasmin
What is the earliest maker of compromised liver function?
Prolonged clotting times
What are the four possible outcomes for patients with acute viral hepatitis B?
Full clinical recovery (virus is rarely completely cleared)
Carrier status
Chronic hepatitis B (some will end up developing cirrhosis and HCC)
Fulminant hepatitis (rare but 80% mortality)
Describe the typical presentation of a patient with obstructive jaundice.
Jaundice RUQ pain Steatorrhoea + dark urine Nausea Raised ALP + GGT
Which investigation can be performed to visualise gallstones?
Biliary ultrasound
Which intervention can be performed to remove gallstones from the CBD and drain pus?
ERCP
Describe the presentation of acute cholecystitis.
Constant, unresolving fever (> 6 hrs)
Tender abdomen
Positive Murphy’s sign
Nausea and (maybe) vomiting
Outline the management of acute cholecystitis.
Antibiotics
NBM
IV fluids
Cholecystectomy
What is Charcot’s triad?
RUQ pain
Jaundice
Fever with rigors
Outline the management of ascending cholangitis.
EMERGENCY Blood cultures Careful monitoring Broad-spectrum antibiotics ERCP if necessary – to drain pus from the CBD
What is Primary Biliary Cirrhosis (PBC)?
Autoimmune disorder characterised by T-cell mediated destruction of the biliary ducts
Which liver enzymes will be deranged in PBC?
High ALP + GGT
Which autoantibody is the hallmark of PBC?
Anti-mitochondrial antibodies (AMA)
Outline the management of PBC.
Confirm diagnosis – MRCP and biopsy Immunosuppression Bile salt replacement Fat-soluble vitamin supplementation Pruritus management – with cholestyramine Liver transplantation
What is Primary Sclerosing Cholangitis (PSC)?
Autoimmune disorder that lead to T-cell mediated destruction of biliary epithelial cells, leading to multifocal scarring of biliary ducts
Which disease is PSC strongly associated with?
Ulcerative colitis
