Jaundice Flashcards
What is jaundice?
- yellow discoloration of skin + sclera
- as a result of hyperbilirubinaemia
- normal range of bilirubin = 3.4-20 umol/L
- jaundice may not be clinically evident until serum levels >50umol/L
- sclera tend to be first to become jaundiced
Describe the metabolism of haemoglobin after red cell breakdown
- bilirubin is a product of metabolism of Hb (80%) and other haem containing proteins (eg. myoglobin, C P450) (20%)
- degradation of Hb into bilirubin takes place in macrophages
- bilirubin is then excreted into plasma and binds w/ albumin
What happens next to the unconjugated bilirubin and how is it excreted?
- uptake of unconjugated bilirubin into hepatocyte
- unconj bilirubin converted to conjugated bilirubin by glucuronyl transferase (makes bilirubin water soluble)
- bilirubin secreted (as component of bile) into small intestine
- bacterial enzymes deconjugate bilirubin and convert it into urobilinogen
- 90% urobilinogen broken down further into stercobilinogen + stercobilin and excreted in faeces
- 10% urobiliniogen absorbed via portal vein
- majoriy of absorbed urobilinogen re-enters hepatocyte + re-excreted in bile (eneterohepatic circulation)
- rest of absorbed urobilinogen bypasses liver and is excreted by kidneys in urine
What can disruption of bilirubin metabolism and excretion lead to?
- hyperbilirubinaemia
- subsequent jaundice
- hyperbilirubinaemia may be unconjugated or conjugated depending on cause
What are examples of unconjugated hyperbilirubinaemias?
- Haemolytic
- Gilbert’s syndrome - UDP-glucuronyl transferase deficiency causing defective conjugation therefore increased unconjugated bilirubin, autosomal recessive, benign
- Crigler-Najjar syndrome - autosomal recessive, deficiency of UDP-glucuronosyl transferase, do not survive to adulthood (T1), type 2 is slightly more common and less severe and may improve w phenobarbital
What are examples of conjugated hyperbilirubinaemias?
- Dubin-Johnson + Rotor syndromes - defective excretion of conjugated bilirubin into biliary cannaliculi therefore elevated conjugated bilirubin
Both are autosomal recessive and benign, get a grossly black liver in Dubin-Johnson syndrome
How is jaundice classified?
- pre-hepatic
- intra-hepatic/hepatocellular
- post-hepatic/obstructive
What are pre-hepatic causes of jaundice?
- Haemolysis
- Gilbert’s syndrome
- Crigler-Najjar syndrome
What are causes of hepatocellular jaundice?
- Alcoholic liver disease
- NAFLD/NASH
- Viral hepatitis
- Autoimmune hepatitis
- Cirrhosis
- Haemochromotosis
- Autoimmune cholangitis
- Wilson’s disease
- Alpha-1-antitrypsin deficiency
- Drug-induced
- Pregnancy
- Malignancy
What are causes of post-hepatic jaundice?
- gallstones
- carcinoma (bile duct, head of panc, ampulla)
- biliary stricture
- sclerosing cholangitis
- pancreatic pseudocyst
- alcohol
- drugs
- cystic fibrosis
What questions are important to ask a jaundiced patient in the history?
- how long? happened before?
- associated symps: fevers? abdo pain? weight loss?
- pale stool, dark urine? (-> obstructive)
- recent foreign travel? country of origin?
- tattoos, IVDU, profession, piercings, blood transfusions, sexual partners?
- alcohol and drug history/intake
- medications?
- family history of jaundice?
- recent surgery?
What clinical features might you look/ask for with a jaundiced patient (examination)?
- hepatomegaly + texture
- splenomegaly
- hepatic encephalopathy
- chronic liver disease stigmata
- lymphadenopathy
- ascites
- palpable gallbladder
- pale stools + dark urine (=cholestatic)
What are differentials for jaundice?
- alcoholic liver disease
- choledocholithiasis
- Hep A, B, C, E
- NASH
- drug-induced
- ascending cholangitis
- autoimmune hep
- pancreatic carcinoma
- haemochromatosis
- pregnancy
- post-op stricture
- haemolysis
- Gilbert’s syndrome
What might be some accompanying symptoms of a patient with jaundice?
- fatigue
- abdominal pain
- weight loss
- vomiting
- fever
- pale stools
- dark urine
How can liver function tests help determine the type of jaundice - specifically conjugated and unconjugated bilirubin?
- Bilirubin (conjugated vs unconj levels) (urine bilirubin and urobilinogen levels)
Total bilirubin and its conjugated and unconjugated levels help to determine nature of jaundice
What other liver function tests apart from bilirubin are useful in determining aetiology of jaundice?
- ALT/AST mainly present in hepatocytes
- ALP/GGT mainly present in biliary tree
- derangement of particular liver enzymes in associated w/ jaundice can determine nature of jaundice
How is urine urobilinogen levels different across pre-hepatic, hepatic and post-hepatic jaundice?
- pre-hepatic: haemolysis results in increased bilirubin prod and subsequent increased bilirubin metabolism and urobilinogen in stool + therefore in urine
- hepatic: some causes result in hepatocellular destruction and therefore reduced re-excretion of re-absorbed urobilinogen (ie. reduction in entero-hepatic circulation of urobilinogen) resulting in elevated levels in urine
- post-hepatic: less bilirubin reaching intestine therefore reduction in urobilinogen therefore reduction in urine urobilinogen
