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 = excessproduction of bilirubin
Hepatic= pathology in hepatocytes or bile cannaliculi in liver
Post-hepatic (obstructive)= blockage of bile ducts outside of liver
What characteristic clinical features are associated with obstructive jaundice?
Dark urine
Pale stools
What are the two causes of cholestatic jaundice?
Obstruction (gallstones)
Paralysis (ileus) of common bile duct = drug induced
What are the two mechanisms of unconjugated hyperbilirubinaemia?
Increased production of bilirubin (increased haemolysis) Decreased capacity to conjugate bilirubin (hepatic pathology)
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
State 2 mechanisms leading to a decreased conjugation of bilirubin
- Reduced unconjugated bilirubin getting into hepatocytes (redcued hepatocyte uptake)
- Decreased conjugation of bilirubin (enzymatic defects)
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 (post ERCP)
- Endocrine – intrahepatic cholestasis of pregnancy
- Degenerative
- Metabolic – haemochromatosis, Wilson’s disease
- Drugs – alcohol, paracetamol, sodium valproate, co-amoxiclav, nitrofurantoin
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 hepatitis of any cause
- Fever and diarrhoea – suggest infection (viral hepatitis)
- Steatorrhoea, dark urine, pruritus – suggests obstructive
- Weight loss, fever, night sweats – systemic features of malignancy (hepatitis, cholgeocarcinoma, pancreatic)
- 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 - obstructive jaundice
- Liver disease
- Haemophilia – may have received contaminated blood products
- Recent blood transfusion or surgery – possible transfusion reaction
- Ulcerative colitis - PSC association
- Diabetes mellitus - haemochromatosis association
- Emphysema - a1- antitrypsin deficiency
- 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, aspirin in G6PD patients
- Autoimmune, extravascular haemolysis: Methyldopa
- Hepatitis: Paracetamol overdose, sodium valproate
- Cholestasis: Co-amoxiclav, nitrofurantoin
List some significant diseases causing jaundice which might be obtained whilst taking the family history
- Gilbert’s
- Haemochromatosis
- Wilson’s Disease
- SCD
- Thalassaemia
- Hereditary spherocytosis
- G6PD
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 (malaria, Hep A+ E East Asia)
List some features that you might see on inspection 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 (haemochromatosis)
- Kayser-Fleischer rings (Wilsons)
List some features you might feel on palpation of someone with Jaundice
- Organomegaly- splenomegaly (extravascular haemolysis), epigastric mass (pancreatic/hepatic malignancy), hepatomegaly (hepatitis)
- RUQ tenderness- Biliary disease, hepatitis
- Ascites- chronic liver disease
- Lymphadenopathy- malignancy
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 (note isolated ALP elevation= increased bone turnover)
What does the finding of bilirubin in the urine indicate?
Post-hepatic obstruction
Which test must be performed in young women presenting with jaundice? List some causes of jaundice in these people
Pregnancy test – there are some causes of jaundice that are exclusive to pregnant women
- pre-eclampsia HELLP syndrome
- Intra-hepatic cholestasis of pregnancy
- Acute fatty liver of pregnancy
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
Why is PTT a better indicator of liver dysfunction than albumin?
- Elevated PTT is one of the earliest signs of liver dysfunction whereas alumin takes 20days to fall
- Low Albumin could be caused by decreased sythesis (hepatic dysfunction) or increased excretion (Nephrotic syndrome)
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 inheritence of Gillbert’s syndrome
Autosomal Recessive
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 => MRCP if inconclusive
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 + analgesia
- NBM
- IV fluids
- Cholecystectomy
What is Charcot’s triad?
Sign of Ascending Cholagitis which is a surgical emergency:
- 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
Explain why a patient with PBC might have a higher brusing tendency?
- Reduced bile outflow
- Vitamin K is a fat soluble enzyme which binds to bile miscelles in the intestines during absorption
- Vitamin K essential for production of clotting factors.
Which liver enzymes will be deranged in PBC?
High ALP + GGT because these are stored within the epithelial cells of the biliary tree. Since these cells are being destroyed, these enzymes will be released
Which autoantibody is the hallmark of PBC?
Anti-mitochondrial antibodies (AMA)
Outline the management of PBC.
- Confirm diagnosis – MRCP and biopsy
- Immunosuppression- corticosteroids, methotrexate, ciclosporin
- Bile salt replacement- urodeoxycholic acid
- 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
Which antibody is often elevated in PSC patients?
pANCA
What Autoimmune screening test is performed for patients with suspected haemolytic anaemia
DAT or Coombe’s test
