Definition: yellow discolouration of skin and sclera as a result of hyperbilirubinaemia



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Definition: yellow discolouration of skin and sclera as a result of hyperbilirubinaemia

  • Definition: yellow discolouration of skin and sclera as a result of hyperbilirubinaemia
  • Bilirubin >35mmol/L for jaundice to be visible on examination
  • Sclera first place to become jaundiced

Bilirubin is a product of metabolism of haemoglobin (80%) and other haem containing proteins (e.g. Myoglboin, cytochrome P450: 20%)

  • Bilirubin is a product of metabolism of haemoglobin (80%) and other haem containing proteins (e.g. Myoglboin, cytochrome P450: 20%)
  • Degredation of haemoglobin into bilirubin takes place in macrophages. Bilirubin is then excreted into plasma and binds with albumin
  • Haemoglobin
  • Globin
  • Haem (iron + porphyrin)
  • Amino Acids
  • Biliverdin
  • Bilirubin (unconjugated)
  • Bilirubin binds to albumin in the plasma
  • RBC breakdown
  • Uptake of unconjugated bilirubin into hepatocyte
  • Unconjugated bilirubin converted to conjugated bilirubin by glucuronyl transferase (this is required before bilirubin can be excreted into the bile, as this process makes bilirubin water soluble)
  • Bilirubin secreted (as component of bile) into the small intestine
  • Bacterial enzymes deconjugate bilirubin and convert it into urobilinogen
    • 90% urobilinogen broken down further into stercobilinogen and stercobilin and excreted in faeces
    • 10% urobilinogen absorbed (via portal vein)
      • Majority of absorbed urobilinogen re-enters hepatocyte and re-excreted in bile (entero-hepatic circulation)
      • The rest of the absorbed urolbilinogen bypasses liver and is excreted by kidneys
  • Disruption of bilirubin metabolism and excretion can cause hyperbilirubinaemia and subsequent jaundice
  • Hyperbilirubinaemia maybe unconjugated (indirect) or conjugated (direct) depending on the cause
  • Some inherited syndromes of bilirubin handling can result in hyperbilirubinaemia
    • Gilbert’s syndrome – reduced activity of glucuronyl transferase therefore reduced conjugated bilirubin therefore elevated unconjugated bilirubin
    • Criggler-Najjar – reduction in amount of glucoronyl transferase therefore elevated unconjugated bilirubin
    • Rotor’s/Dubin-Johnson syndrome – defective excretion of conjugated bilirubin into the biliary cannaliculi therefore elevated conjugated bilirubin

Pre-hepatic: pathology occuring prior to the liver

  • Pre-hepatic: pathology occuring prior to the liver
      • Any cause of increased haemolysis (e.g. Spherocytosis, thalassaemia, sickle cell disease, transfusion reaction, auto-immune, malaria etc.) and some drugs
      • Causes unconjugated hyperbilirubinaemia
  • Intra-Hepatic: pathology occuring within the liver
      • All the causes of hepatitis/cirrhosis (e.g. Alcohol, viral, auto-immune, primray biliary cirrhosis, haemochromatosis, wilsons, alpha-1 antitrypsin deficiency etc.), inherited condition on previous slide and some drugs
      • Can result in hepatocyte destruction and therefore unconjugated hyperbilirubinaemia or in bile cannaliculi destruction and therefore conjugated hyperbilirubinaemia or both
      • Note/ neonatal jaundice: occurs in most newborns as hepatic machinary for conjugation and excretion of bilirubin not fully matured until 2 weeks of age
  • Post-hepatic: pathology occuring after conjugation of bilirubin within the liver (aka obstructive jaundice)
      • Any cause of biliary obstruction (e.g. Gallstones)
      • Causes conjugated hyperbilirubinaemia

Following investigations will help to determine nature of jaundice:

  • Following investigations will help to determine nature of jaundice:
  • Liver function tests
      • Bilirubin
      • ALT/AST
      • ALP/GGT
  • Conjugated v Unconjugated bilirubin levels
  • Urine bilirubin and urobilinogen levels
  • Test
  • Pre-hepatic
  • Hepatic
  • Post-hepatic
  • Total bilirubin
  • +
  • ++
  • +++
  • Conjugated bilirubin
  • Normal
  • Increased
  • Increased
  • Unconjugated bilirubin
  • Increased
  • Increased
  • Normal
  • Total bilirubin and its conjugated and unconjugated levels help to determine nature of jaundice

Liver Enzymes

  • Liver Enzymes
      • ALT/AST mainly present in hepatocytes
      • ALP/GGT mainly present in bile cannaliculi biliary tree
  • Derrangement of particular liver enzymes in association with jaundice can determine nature of the jaundice
  • Test
  • Pre-hepatic
  • Hepatic
  • Post-hepatic
  • ALT/AST
  • Normal
  • +++
  • +
  • ALP/GGT
  • Normal
  • +
  • +++

Urine bilirubin

  • Urine bilirubin
        • Normally, tiny amount bilirubin (conjugated) excreted in urine
        • Pre-hepatic jaundice: Haemolysis causes rise in unconjugated bilirubin (water insoluble) and this is not excreted by the kidney therefore there is no rise in urine bilirubin
        • Some causes of Hepatic jaundice: result in damage to biliary cannaliculi and therefore result in poor biliary drainage and therefore elevated conjugated bilirubin levels in blood, excreted into urine (giving dark urine)
        • Post-Hepatic juandice: Obstruction to biliary drainage and so conjugated bilirubin (water soluble) levels in the blood increase and appear in the urine (giving dark urine)
  • Urine urobilinogen
        • Pre-hepatic jaundice: Haemolysis results in increased bilirubin production and subsequent increase bilirubin metabolism and urobilinogen in stool and therefore in the urine.
        • Some causes of Hepatic jaundice : result in hepatocellular destruction and therefore reduced re-excretion of re-absorbed urobilinogen (i.e. Reduction in entero-hepatic circulation of urobilinogen) resulting in elevated levels in urine
        • Post-Hepatic jaundice: Less bilirubin reaching intestine therefore reduction in urobilinogen therefore reduction in urine urobilinogen
  • Test
  • Pre-hepatic
  • Hepatic
  • Post-hepatic
  • Urine Bilirubin
  • negative
  • Negative (but maybe increased depending on cause)
  • Increased
  • Urine urobilinogen
  • Increased
  • Normal (but maybe increased depending on cause)
  • Decreased/negative
  • Urine colour
  • Normal
  • Normal (but maybe dark depending on cause)
  • Dark
  • Stool colour
  • Normal
  • Normal
  • Pale

How long been jaundiced?

  • How long been jaundiced?
  • Ever been jaundiced before?
  • Any associated fevers or abdominal pain or weight loss?
  • Pale stool and dark urine (suggests obstructive/post-hepatic jaundice)?
  • Any recent foreign travel (hepatitis, malaria)?
  • Any risk factors for hepatitis (tattoos, IVDU, high risk professions, blood transfusions, multiple sexual partners)?
  • PMH of blood disorders (e.g. SCD, thalassemia)?
  • DH any new medications that can cause jaundice?
  • SH excess alcohol intake
  • FH of jaundice (inherited disorders of bilirubin metabolism)

If jaundice associated with background of intermittent RUQ pains think gallstones and choledocholithiasis

  • If jaundice associated with background of intermittent RUQ pains think gallstones and choledocholithiasis
  • If jaundice associated with long history of upper abdominal pain and weight loss and patient elderly thing pancreatic cancer
  • If jaundice associated with recent foreign travel think hepatitis (A,E) or malaria
  • If jaundice occuring in patient with risk factors think hepatitis B,C
  • If jaundice occuring on a background of alcohol abuse think alcoholic liver disease
  • If jaundice is painless and family history of blood disorder think pre-hepatic jaundice

Blood tests

  • Blood tests
      • FBC (low HB suggesting haemolysis
      • LFTs (bilirubin, ALT/AST, ALP/GGT, albumin)
      • Conjugated and unconjugated bilirubin
      • Clotting (INR)
      • U&E (hepatorenal syndrome)
  • Urine
      • Bilirubin
      • Urobilinogen
  • Above tests used to determine if jaundice pre/intra/post hepatic which will determine further investigations

Pre-hepatic

  • Pre-hepatic
      • Sickle cell test
      • Serum electrophoresis
      • Blood film
  • Hepatic
      • Serum iron, ferritin, copper, alpha-1 antitrypsin levels
      • auto-antibody screen
      • Hepatitis screen
      • Liver USS
  • Post-hepatic
      • As surgeons we deal with post-hepatic jaundice

Causes

  • Causes
      • Luminal
          • Gallstone
      • Intra-mural
          • Benign stricture (e.g. As complication of cholecystectomy or due to pancreatitis)
          • Malignant stricture: cholangiocarcinoma
      • Extra-mural
          • Head of pancreas cancer
          • Pancreatitis (oedema of head of pancreas)
          • Pancreatic pseudocyst
          • Compression by malignant lymph nodes at porta hepatis

Blood tests

  • Blood tests
      • FBC (elevated WCC in ascending cholangitis)
      • U&E (monitor renal function in case of hepato-renal syndrome)
      • LFTs (elevated bilirubin, ALP/GGT)
      • Conjugated/unconjugated bilirubin
      • Clotting (INR maybe elevated)
  • USS
      • Look for gallstones, biliary tree dilatation, stone in CBD (though often not seen due to bowel gas).
      • Look at pancreas to look for cancer (often poor views due to overlying bowel gas)
      • Look at liver to exclude parenchymal disease.

PTC (percutaneous transhepatic cholangiogram) – performed by interventional radiologist

  • PTC (percutaneous transhepatic cholangiogram) – performed by interventional radiologist
      • Diagnostic and therepeutic (biliary drain to relieve obstruction) but invasive
      • More invasive and Higher complication rate than ERCP (particularly haemorrhage) therefore used in situations where ERCP unavailable (out of hours in patient with cholangitis) or unsuccesful

Monitor for acute renal failure (hepato-renal syndrome)

  • Monitor for acute renal failure (hepato-renal syndrome)
      • Ensure patients well fluid resuscitated and monitor urine output to reduce the risk of the above
  • Monitor INR
      • If derranged give vitamin K
  • Determine cause of obstructive jaundice
  • Danger is progression to ascending cholangitis (Charcot’s triad) – can be life threatening!
      • Must un-obstruct Biliary tree to prevent development of cholangitis

ERCP preferred method

  • ERCP preferred method
      • Balloon trawl or dormia basket (for stones)
      • Sphincterotomy (to prevent future stones from obstructing)
      • Stent (to allow free drainage of bile past a stricture)
  • PTC
      • Used where ERCP unavailable or unsuccesful (as more invasive and higher complication rate)
      • Drain inserted percuteously, trans-hepatically (through the liver) and into the biliary tree to allow free drainage of bile
  • Questions?


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