14. Jaundice Flashcards
What 3 steps can bilirubin metabolism be summarised into?
Production of unconjugated bilirubin
Conjugation of bilirubin
Excretion of bilirubin
What is prehepatic jaundice?
Jaundice caused by excessive production of BR
Extravascular + intravascular
What is hepatic jaundice?
Jaundice due to pathology in the liver (hepatocytes + bile canaliculi)
What is posthepatic jaundice?
Jaundice caused by problems with biliary flow
What is obstructive jaundice?
Jaundice caused by lack of bile flow into the gut
Results in pale faeces (lack of urobilin/stercobilin) + dark urine (conjugated BR)
What is cholestatic jaundice?
Jaundice caused by BR not flowing out the common bile duct
Can be due to gallstones, ileus or CBD peristalsis (drug induced)
What is unconjugated jaundice?
Jaundice caused by accumulation of unconjugated BR
Due to excessive production of unconjugated BR or decreased capacity to conjugate BR
What causes increased production of bilirubin?
Intravascular haemolysis
Congenital: G6PD, PKD, SCD + thalassemia
Acquired: artificial heart valves, DIC, malaria
Extravascular haemolysis
Congenital: hereditary spherocytosis
Acquired: AI haemolysis
What causes decreased conjugation of bilirubin?
Decreased hepatocyte uptake: contrast agents + portosystemic shunts to bypass a cirrhotic liver
Congential enzymatic problems: Gilbert’s
What causes decreased excretion of bilirubin?
INVITED MD
Infection: hepatitis, ascending cholangitis, liver abscess
Neoplastic: mets, HCC, cholangiocarcinoma + pancreatic
Vascular: Budd chiari syndrome
Inflammation: PBC, PSC, AI hepatitis, pancreatitis
Trauma: gallstones, stricture after ERCP
Endo: intraheptic cholestasis of pregnancy
Degenerative: none
Metabolic: Wilson’s, haemachromatosis
Drugs: some affect ability of hepatocytes to excrete BR- alcohol, paracetamol, valproate + rifampicin. Some cause biliary ileus: nitrofurantoin, OCP
What questions should you ask in the presenting complaint in someone with jaundice?
Acute/ chronic?
Pregnant?
Associated symptoms:
RUQ pain, N+V, pruritus (hepatitis)
Fever or diarrhoea (viral hepatitis/ abscess)
Steatorrhoea, dark urine, pruritus (obstructive jaundice)
Weight loss, fever, night sweats (malignancy)
Bronzed skin + DM (haemochromatosis)
Exposure to outdoor water/ sewage (risk factor for leptospirosis)
What should you ask in the PMHx in someone with jaundice?
Gallstones Liver disease Haemophilia Recent blood transfusion/ surgery Ulcerative colitis Diabetes Emphysema (suggests alpa 1 antitrypsin deficiency)
What should you ask about in the social history in someone with jaundice?
Excessive alcohol consumption IV drug use Unprotected sex/ multiple partners Foreign travel Tattoos
What physiological processes occur in production of unconjugated BR?
RBCs broken down by macrophages in spleen
Hb degraded into iron + insoluble BR
Insoluble BR travels to liver bound to albumin
What physiological processes occur in conjugation of BR?
Hepatocytes uptake unconjugated BR
Conjugate to glucuronate making it water soluble
What physiological processes occur in excretion of BR?
Conjugated BR secreted into bile canaliculi
Flows with bile into duodenum
Metabolised by bacteria into colourless urobilinogen + stercobilinogen
Some reabsorbed in gut + excreted via kidneys
Majority oxidised in gut to coloured pigments (urobilin + stercobilin) giving faeces its brown colour
What is conjugated jaundice?
accumulation of conjugated BR
By what 4 mechanisms can drugs cause haemolysis?
Intravascular: Sulphonamides
AI, extravascular: Methyldopa
Hepatitis: Paracetemol OD
Cholestasis: Co-amoxiclav
What 7 familial conditions can cause jaundice?
Gilbert's syndrome Haemochromatosis Wilson's disease Sickle cel disease Thalassaemia Hereditary spherocytosis G6PDH deficiency
What is haemochromatosis?
Deficiency of iron regulatory hepcidin.
Allows increased intestinal absorption of iron causing accumulation in tissues, esp. the liver, which may lead to organ damage.
What is Gilbert’s syndrome?
Defected gene for conjugating enzyme
Results in unconjugated hyperbilirubinaemia
What is usually the cause of elevated AST > ALT?
Excessive alcohol intake
What is usually the cause of elevated ALT > AST?
Viral hepatitis
In which 3 situations may you see AST and ALT elevated into the 1000s?
Viral hepatitis
Paracetamol OD
Ischaemic hepatitis
What is suggested by a raised ALP and GGT?
Bile duct pathology (obstruction)
What is suggested by a raised ALP and normal GGT?
Increased bone turnover (malignant bone mets, primary hyperparathyroid)
What is suggested by a raised GGT in isolation?
Recent alcohol consumption
What does bilirubin in the urine signify?
Posthepatic jaundice
Which antibodies should you include in an autoimmune screen for cause of jaundice with raised liver enzymes?
Antinuclear antibodies (ANA) Antismooth muscle antibodies (ASMA): Type 1 AI hepatitis Antimitochondrial antibodies (AMA): PBC + some AI hepatitis
What pathophysiological process occurs in PBC?
AI destruction of the small interlobular bile ducts
Causes intrahepatic cholestasis which damages cells, leading to scarring, fibrosis + eventually cirrhosis.
What is PSC? What condition is this strongly associated with)
Chronic cholestatic disorder characterised by inflammation + fibrosis of intra- + extrahepatic bile ducts, resulting in multifocal biliary strictures.
UC
What is cholelithiasis?
Stones in gallbladder
What is Cholecystitis?
Inflammation of gallbladder + cystic duct
What is Choledocholithiasis?
Stones in the common bile duct
What is Cholangitis?
Inflammation of bile ducts/ biliary system
