Jaundice Flashcards
Define jaundice
- yellowing of the skin, sclera and mucosa from an increase in plasma bilirubin
At what level of plasma bilirubin does jaundice become visible
visible at > 60umol/L
Describe how bilirubin is broken down
- bilirubin is conjugated with glucuronic acid by hepatocytes making it water soluble
- conjugated bilirubin is secreted into bile and passes into gut
- some is taken up by the liver again (enterohepatic circulation) and the rest is converted to urobilinogen by gut bacteria
- Urobilinogen is then either reabsorbed and excreted by the kidneys or converted into stercobilin which colours the faeces brown
What are the two cases of jaundice
- Unconjugated hyperbilirubinaemia - water insoluble so does not enter urine
- Conjugated hyperbilirubinaemia - water soluble so enters the urine and makes the urine dark, less conjugated bilirubin enters the gut (due to cholestasis) and the faeces become pale
Describe the pathophysiology of pre hepatic jaundice
- excess red blood cell breakdown overwhelms the livers ability to conjugate bilirubin this leads to unconjugated hyperbilirubinaemia
- this is not water soluble so cannot be excreted into the urine
- intestinal bacteria convert some of the extra bilirubin into urobilinogen which is reabsorbed and is excreted by the kidney therefore urinary urobilinogen is increased
Name the pre-hepatic cause of jaundice
Congenital RBC issues Cell shape - sickle cell disease - hereditary spherocytosis - hereditary elliptocytosis Enzyme - GP6D deficiency - pyruvate kinase deficiency Haemoglobin - thalassaemia
Autoimmune haemolytic anaemia
Drugs
- penicillin
- sulphasalazine
- antimalarials
Infections
- malaria
Mechanical
- metallic valve prostheses
- DIC
transfusion reaction s
paroxysmal nocturnal haemoglobinuria
describe the pathophysiology of hepatocellular causes of bilirubin
- disorders of uptake, conjugation or secretion of bilirubin leading to mixed conjugated and unconjugated hyperbilirubinaemia
name the conjugated causes of hepatocellular jaundice
- cirrhosis
- malignancy - primary or metastases
- viral hepatitis
- Drugs
- Enzymes
Name the drugs that can cause hepatitis
- isoniazid
- rifampicin
- atenolol
- enalapril
- verapamil
- nifedipine
- amiodarone
- ketoconazole
- cytotoxic
- halothane
What drugs cause cholestasis
- ciclosporin
- azathioprine
- chlorpromazine
- cimetidine
- erythromycin
- nitro
- ibuprofen
- hypoglycaemics
What is Dubin-Johnson syndrome
- Autosomal recessive (cMOAT gene) with excretion of conjugated bilirubin – leads to pigmented liver
- Increase in conjugated bilirubin with no other enzyme changes
- High coproporphyrin
What is Rotor syndrome
- Similar to DJS
- Liver not pigmented
- Normal coproporphyrin
Name the unconjugated causes of hepatocellular jaundice
- Gilbert’s syndrome
- Crigler-Najjar syndrome
What is Gilbert’s syndrome
- Congenital hypo-activity of conjugation enzyme UGT-1; benign and common (5%)
- Normal LFTs except mildly elevated bilirubin, especially in times of physiological stress/illness
- Normal life expectancy; benign condition
What is Crigler-Najjar syndrome
- autosomal recessive (type I) or dominant (type II)
- congenial absence in type 1 or decrease of glucoronyl transferase in type 2
- leads to severe unconjugated hyperbilirubinaemia
- normal liver histology
- treatment is liver transplant; only type II survive to adulthood
Describe the pathophysiology of post hepatic jaundice
- obstruction of biliary drainage - this leads to conjugated hyperbilirubinaemia
Name the causes of post hepatic jaundice
- Hillary tree obstruction
- primary biliary cirrhosis (ANA and anti-microbial Abs)
- primary sclerosis cholangitis (ANCA, anti-smooth muscle Abs, 80% have UC, association with cholangiocarcinoma)
- Drugs
what can cause biliary tree obstruction
- common bile duct gallstones
- compression of the bile duct e.g. pancreatitis, pancreatic cancer, lymph nodes, biliary atresia
- cholangiocarcinoma
- post-operative stricture
- choledochal cyst
- Caroli’s disease
- Mirizzi’s syndrome
What is Caroli’s syndrome
multiple segmental cystic or saccular dilatations of intrahepatic bile ducts with congenital hepatic fibrosis; may present in 20yo with portal HTN ± recurrent cholangitis/cholelithiasis
What is Mirizzi’s syndrome
common bile duct compression by a gallstone impacted in the cystic duct, often associated with cholangitis
What are the drugs that can cause obstruction of biliary drainage
- flucloxacillin
- fusidic acid
- Co-amoxiclav
- nitrofurantoin
- steroids
- sulfonylureas
- prochlorperazine
- chlorpromazine
What are the causes of jaundice in a previously stable patient with cirrhosis
- Sepsis (UTI, pneumonia, peritonitis)
- malignancy (hepatocellular carcinoma)
- alcohol
- Drugs
- GI bleeding
What should you ask in a history of a patient that is jaundice
- blood transfusions
- IV drug use
- body piercing
- tattoos
- sexual activity
- travel
- jaundiced contacts
- family history
- alcohol use
- ALL medications - old drug charts, GP records
What should happen in an examination of a jaundice patient
- signs of chronic liver disease
- hepatic encephalopathy
- lymphadenopathy
- hepatomegaly
- splenomegaly
- ascites
- palpable gallbladder - if seen with painless jaundice the cause is not gallstones - more likely pancreatic or gallbladder cancer as stones lead to fibrotic unexpandable gallbladder
- pale stools and dark stools - cholestatic jaundice
What should you check the urine for in jaundice patients
- Prehepatic causes (unconjugated): absent bilirubin
- obstructive causes (conjugated): absent urobilinogen
What should be in the haematology in a jaundice patient
- FBC
- Clotting film
- Reticulocyte count
- Coombs’ test
- Haptoglobins for haemolysis
- Malaria parasites (e.g. if unconjugated hyperbilirubinaemia/fever)
- Paul Bunnell (suspected EBV)
what should you check in chemistry in a jaundice patient
- U&Es
- LFT
- total protein
- serum albumin
- paracetamol level
What microbiology should be tested in a jaundice patient
- blood and other cultures
- hepatitis serology
What imaging should be used in a jaundice patient
- Ultrasound – Are bile ducts dilated? Are there gallstones, metastases, or a pancreatic mass?
- ERCP – If bile ducts are dilated and LFTs not improving
- MRCP or EUS – if US shows gallstones but no definite common bile duct stones
- Liver biopsy – If bile ducts are normal
- CT/MRI abdo – if abdominal malignancy is suspected
What causes unconjugated hyperbilirubinemia
- water insoluble so does not enter the urine
- Gilbert’s syndrome – mutation of UGT-1
- Crigler Najjar syndrome – split into type 1 (autosomal recessive) and type 2(autosomal dominant), only type 2 survive till adulthood -leads to congenial absence in type 1 or deficiency in type 2 of glucornyl transferase – treatment is liver transplant
- Overproduction – haemolysis, ineffective erythropoiesis
- Impaired hepatic uptake – drugs, ischaemic hepatitis
- Impaired conjugation – Gilberts and Crigler Najjar
- Physiological neonatal jaundice
What causes conjugated hyperbilirubinaemia
- water soluble so enters the urine and makes the urine dark
- Hepatocellular dysfunction – hepatocyte damage, virus hepatitis, autoimmune hepatitis, alpha 1-antirypsin deficiency, Wilsons disease, Dubin Johnson and Rotor syndrome, haemochromatosis
- Impaired hepatic excretion – BC, PSC, drugs, common bile duct obstruction, Mirrizi syndrome
