Jaundice and Bilirubin Flashcards
What is jaundice?
Yellow pigmentation of the skin or sclerae, caused by high levels of unconjugated or conjugated bilirubin in the blood
When is jaundice clinically apparent?
Plasma bilirubin concentration >50uM/L
Where is bile stored and concentrated?
Gallbladder
What causes bile to be released?
- CCK (cholecystokinin)
- Vagal response to food
What is bile composed of?
- Bile pigments (Hb breakdown products)
- Bile salts (derived from cholesterol and help emulsify fat)
What is bilirubin?
Hb breakdown product
Give an overview of bilirubin metabolism:
- Formed as a breakdown product of haemoglobin
- Conjugated in the liver to form a water-soluble molecule
- Extricated in the bile
- Metabolised in the gut by bacteria into urobilinogen and stercobilin
- Urobilinogen is reabsorbed and excreted in the liver
What is pre-hepatic jaundice?
Unconjugated hyperbilirubinemia
- Excess production of bilirubin that overtakes the ability of liver to conjugate the bilirubin and excrete into the gut
What can cause pre-hepatic jaundice?
o Haemolytic anaemia o RBC abnormality (sickle cell) o Incompatible blood transfusion o Drug reaction o Hypersplenism
What are the symptoms of pre-hepatic jaundice?
- Skin yellowing
- Pale urine
unconugated bilirubin is water-insoluble so does not enter urine - Dark stools (normal)
What is the reason for the symptoms in pre-hepatic jaundice?
- Liver function in patients with haemolytic jaundice is normal, but because of increased RBC breakdown, glucuronyl transferase is saturated.
- The liver compensates by increasing conjugated bilirubin output, making the stools dark (normal).
- This unconjugated bilirubin cannot be excreted in urine as it is not water soluble, so there is little/no bilirubin the urine causing pale urine
What is hepatic jaundice?
Conjugated and unconjugated hyperbilirubinemia
- Due to parenchymal liver disease (Intrinsic abnormality of the hepatocyte) with inability to either conjugate, uptake or excrete bilirubin.
What can cause hepatic jaundice?
- Congenital
- Acquired
Infection (viral hepatitis)
Cirrhosis (alcohol)
Cirrhosis (NASH)
Damage by toxins or drugs
What are the symptoms of hepatic jaundice?
- Skin yellowing
- Variable Dark urine
- Variable Pale stools
In hepatocellular damage what would the LFTs show?
INCREASED:
- ALT (markedly)
- AST
- GGT
- Bilirubin
- Alk. phos (mildly)
- INR
Rise in ALT, AST»_space; rise in alk phos
DECREASED:
- Albumin
What would you find on examination with hepatic jaundice?
- Dull RUQ pain
- US: liver enlarged/shrunken with or without splenomegaly
What is post-hepatic jaundice?
An impediment to the flow of bile due to a partial or complete obstruction of the extrahepatic biliary passage between the liver and duodenum.
What can cause post-hepatitc jaundice?
• Obstruction of bile duct by stone
• Obstruction of bile duct by tumour
Head of pancreas
Cholangiocarcinoma
Lymph Node metastasis
• Also consider intra-hepatic cholestasis
Primary biliary cholangitis
Primary sclerosing cholangitisWhat is cholestasis?
A decrease in bile flow due to impaired secretion by hepatocytes or to obstruction of bile flow through intra-or extrahepatic bile ducts.
What are the symptoms with post-hepatic jaundice?
- Skin yellowing
- Dark urine
Liver fucntion is normal, so bile is conjugated - Pale stools
No bilirubin in intestine
In post-hepatic jaundice what would the LFTs show?
INCREASED:
- ALT (mildly)
- AST
- ALP (markedly)
- INR (maybe)
can be correctable with Vitamin K
- Bilirubin
Rise in ALT, AST «_space;rise in alk phos
UNCHANGED:
- Albumin
What would you find on examination with post-hepatic jaundice?
- Colicky RUQ pain
Pain that stops and starts abruptly - US/CT: cholelithiasis, dilated biliary tree, SOL (space occupying lesions), gallbladder stones
- Pruritis
When is neonatal jaundice detectable?
Serum bilirubin > 85 micromoles/litre
Which type of jaundice is more common in newborns?
Unconjugated hyperbilirubinaemia
Which type of jaundice is toxic in newborns and why?
Unconjugated hyperbilirubinaemia
- Can penetrate the blood-brain barrier
- Stains neurological tissue, causing kernicterus (brain damage)
- Causes bilirubin encephalopathy
How do you prevent neonatal jaundice from worsening?
- Fluid and caloric intake
How do you treat neonatal unconjugated hyperbilirubinaemia?
- Phototherapy
Light treatment breaks down bilirubin molecules - Exchange transfusion
How do you treat neonatal conjugated hyperbilirubinaemia?
- Manage the obstruction
What would you look for in the history of an adult with jaundice?
• Drug and alcohol Hx
• Cigarette use
• Foreign travel
• Sexual Hx
Association with Heb B and obstructive jaundice
• Colour of urine and stools
• Duration
• Jaundice with or without pain
Painless = classic symptom of pancreatic cancerWhat investigations would you order for jaundice?
- FBC
Infection?
- Urea and electrolytes
Renal impairment
- LFTs
- Clotting screen
- Amylase
If pancreatitis is suspected
- Hep A, B and C
If risk factors present
- Urine dipstick
Indicates increased conjugated bilirubinIf obstructive jaundice is NOT suspected, what tests would you order?
- Viral hepatitis screen
hepatitis A, B, and C. - Immunoglobulins.
- Auto-antibody profile
High levels of IgM are characteristic of primary Biliary cholangitis
High levels of IgG indicate chronic active hepatitis.
ANA/SMA/LKM1 antibodies, raised IgG levels in autoimmune hepatitis - Ferritin (and transferrin saturation if ferritin is raised)
Screen for hereditary haemochromatosis. - Alpha1-antitrypsin.
- Alpha-fetoprotein
Increased levels may indicate hepatocellular carcinoma. - Caeruloplasmin.
- Thyroid function tests
What would you identify in a focused history for jaundice?
• Drug and alcohol Hx
• Cigarette use
• Foreign travel
• Sexual Hx
Association with Heb B and obstructive jaundice
• Colour of urine and stools
• Duration
• Jaundice with or without pain
Painless = classic symptom of pancreatic cancerWhat might you see in an examination for jaundice?
• Sclera and skin
• Scratches from puritis/itching (bilirubin breakdown can cause itching)
• Evidence of weight loss (thenar wasting)
Indication that underlying jaundice is due to malignancy
Troisier’s node (left supraclavicular node enlargement)
o Indication that underlying jaundice is due to malignancy
What are the red flags for jaundice?
• Hepatic encephalopathy:
Confusion or alteration in mental state
Altered neuromuscular function
- Poor coordination
- Ataxia
- Asterixis
- Nystagmus
• Hepatic dysfunction
Bruising, purpura or petechiae
• GI blood loss
Haematemesis or melaena
• Sepsis
Fever, hypotension and tachycardia
• Marked abdominal tenderness or pain
• Vomiting
• Suspected paracetamol overdoseWhat does bile leave the liver through?
Common hepatic duct
How does bile get into the gallbladder?
Cystic duct
When bile is released from the gallbladder, what does it travel through?
Common bile duct
