Jaundice
description
Transcript of Jaundice
Mohammad MobasheriSpR General Surgery
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%) 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 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:
Liver function tests Bilirubin ALT/AST ALP/GGT
Conjugated v Unconjugated bilirubin levels Urine bilirubin and urobilinogen levels
Test Pre-hepatic Hepatic Post-hepaticTotal 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 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-hepaticALT/AST Normal +++ +ALP/GGT Normal + +++
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 urobilinogenTest 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? 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 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 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 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 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 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
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)
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 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?